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Clinical Policy Title: Skin substitutes – bioengineered

Clinical Policy Number: 16.03.09

Effective Date: May 1, 2018

Initial Review Date: March 6, 2018

Most Recent Review Date: April 10, 2018

Next Review Date: April 2019

Related policies:

CP# 16.02.02 Growth factors for wound healing

CP# 16.03.03 Negative pressure wound therapy

CP# 18.02.01 Full body hyperbaric oxygen therapy

ABOUT THIS POLICY: AmeriHealth Caritas has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas’ clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of “medically necessary,” and the specific facts of the particular situation are considered by AmeriHealth Caritas when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas’ clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas’ clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, AmeriHealth Caritas will update its clinical policies as necessary. AmeriHealth Caritas’ clinical policies are not guarantees of payment.

Coverage policy

AmeriHealth Caritas considers bioengineered skin substitutes (herein referred to as “skin substitutes”)

for the treatment of pressure ulcers to be not clinically proven and, therefore, investigational (National

Pressure Ulcer Advisory Panel, 2014).

AmeriHealth Caritas considers skin substitutes to be clinically proven and, therefore, medically

necessary for treatment of chronic wounds in members who meet the following criteria (Interqual,

2017; Game, 2016):

Ages 18 years or older.

Full or partial thickness skin defect, clean and free of necrotic debris, exudate, or infection.

Tissue approximation would cause excessive tension or functional loss.

For diabetic foot ulcers and venous stasis ulcers, failure to respond to at least 30 days of

standard of care conservative therapy. Failed response is defined as an ulcer or skin deficit

Policy contains:

Skin substitutes.

Diabetic foot ulcers.

Venous stasis ulcers.

Pressure ulcers.

Thermal burns.

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that has failed to respond to documented appropriate wound-care measures, has

increased in size or depth, or has not changed in baseline size or depth and has no

indication that improvement is likely (such as granulation, epithelialization or progress

towards closing) (Medicare Local Coverage Determination [LCD] L35041).

Meets all wound-specific criteria and product-specific criteria below (see also Appendix).

For diabetic foot ulcers, when all criteria are met (Interqual, 2017; Hingorani, 2016; Lavery, 2016;

Medicare LCD36466):

At least 1.0 cm2 in size.

Partial or full thickness ulcers that extend through the dermis, but does not involve any

tendon, muscle, joint capsule, or bone exposure, with a clean granular base.

Has been present for at least four weeks.

Adequate circulation in affected extremity by physical examination or imaging (e.g.,

palpable dorsalis pedis or posterior tibial artery pulse or an ankle brachial index ≥ 0.60).

Under current diabetes medical management (including nutritional support and neuropathy

treatment) with evidence of stable glycated hemoglobin levels.

Applied in conjunction with conservative therapy (e.g., moist wound environment with

dressings or non-weight bearing or pressure reduction interventions).

For venous stasis ulcers, when all criteria are met (Interqual, 2017; Marston, 2016; O’Donnell, 2014;

Medicare LCD36466):

At least 1.0 cm2 in size.

Partial- or full-thickness ulcer.

Has been present for at least three months.

Adequate circulation in affected extremity by physical examination or imaging (e.g.,

palpable dorsalis pedis or posterior tibial artery pulse or an ankle brachial index ≥ 0.60).

Under current medical management for venous insufficiency, with objective documentation

that supports the diagnosis.

Applied in conjunction with conservative therapy (e.g., compression wraps).

For partial- or full-thickness thermal burns when both criteria are met (Interqual, 2017; Wasiak, 2013):

Excision of the burn wound is complete (e.g., nonviable tissue is removed) and homeostasis

is achieved.

Sufficient full-thickness autograft tissue is not feasible at the time of excision.

AmeriHealth Caritas considers the following skin substitutes to be clinical proven and, therefore,

medically necessary when used in accordance with U.S. Food and Drug Administration (FDA) approval

or regulation as human cells, tissue, and cellular and tissue-based products, and in accordance with

the product labeling instructions (See Appendix for complete details):

AMNIOEXCEL® (Derma Sciences Inc., Princeton, New Jersey).

Apligraf® (Graftskin) (Organogenesis Inc., Canton, Massachusetts).

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Biobrane® (UDL Laboratories Inc., Rockford, Illinois).

Dermagraft® (Organogenesis Inc., Canton, Massachusetts).

EpiFix® (Mimedx Group, Inc., Marietta, Georgia).

Grafix® (Osiris Therapeutics, Inc., Columbia, Maryland).

GRAFTJACKET TM Regenerative Tissue Matrix (Wright Medical Technology Inc., Arlington,

Tennessee).

Hydron® (Abbott. Laboratories, Abbott Park, Illinois).

Integra® Bilayer Matrix (Lifesciences Corporation, Plainsboro, New Jersey).

OASIS® Wound Matrix (Cook Biotech Inc., West Lafayette, Indiana).

Orcel® (Ortec International, Inc., New York, New York).

Suprathel® Wound and Burn Dressing (PolyMedics Innovations, GmbH, Germany).

Talymed® (Marine Polymer Technologies, Inc., Danvers, Massachusetts).

Transcyte™ (Shire Regenerative Medicine, San Diego, California).

Limitations:

New products and clinical applications continue to emerge. Skin substitutes that are not listed in the

Appendix lack supportive evidence from randomized controlled trials, but they may be approved on a

case-by-case basis if their intended use is consistent with regulatory requirements and product-specific

labeling.

Contraindications to skin substitutes include (Hingorani, 2016; Lavery, 2016; International Society for

Burn Injury, 2016; Marston, 2016; O’Donnell, 2014; See Medicare LCDs):

Inadequate control of underlying conditions or exacerbating factors (e.g., uncontrolled

diabetes, active infection, and active Charcot arthropathy of the ulcer extremity, vasculitis,

or continued tobacco smoking without physician attempt to effect smoking cessation).

Known hypersensitivity to any component of the specific skin substitute graft (e.g., allergy to

avian, bovine, porcine, piscine, or equine products).

All other uses of the skin substitutes listed in the Appendix are not medically necessary, including, but

not limited to (Medicare L36377, L36466, and L36690):

Skin grafting or replacement for partial thickness loss with the retention of epithelial

appendages, as epithelium will repopulate the deficit from the appendages, negating the

benefit of over-grafting.

Simultaneous use of more than one product for the episode of wound. Product change

within the episode of wound is allowed, not to exceed 10 applications per wound per 12-

week period of care.

Repeat or alternative applications of skin substitute grafts when a previous full course of

applications was unsuccessful. Unsuccessful treatment is defined as increase in size or depth

of an ulcer or no change in baseline size or depth, and no sign of improvement or indication

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that improvement is likely (such as granulation, epithelialization, or progress towards

closing) for a period of four weeks after the start of therapy.

Re-treatment of healed ulcers, those showing greater than 75 percent size reduction, and

those smaller than 0.5 cm2.

Re-treatment within one year of any given course of skin substitute treatment for a venous

stasis ulcer or diabetic foot ulcer, as such re-treatment is considered treatment failure.

The success of the procedure is somewhat dependent on the skill of the performing provider; therefore,

the provider may be subject to a post-payment peer review to verify his or her qualifications.

Debridement and ulcer/wound preparation are considered a part of the material application procedure.

Repeat use of surgical preparation services (CPT codes 15002, 15003, 15004, and 15005) in conjunction

with skin substitute application codes is not medically necessary. It is expected that each wound will

require the use of appropriate wound preparation code at least once at initiation of care prior to

placement of the skin substitute graft.

For Medicare members only:

Medicare Part B accepts the FDA classification and description of any skin substitute. The FDA has

regulated most skin substitutes as medical devices. However, some are regulated as human tissue and

are, therefore, subject to the rules and regulations of banked human tissue, not the FDA approval

process (L34285; L35041; L36377; L36466; L36690; National Coverage Determination [NCD] 270.5).

The following indications and limitations to Medicare coverage and payment apply to the specified skin

substitute and their related application physician services. Unless otherwise indicated, Medicare

considers the following products to be reasonable and medically necessary for treatment of diabetic

foot ulcers and venous stasis ulcers, as well as diabetic ulcers of the ankle and calf (L34285):

Apligraf (Q4101) — Payment is limited to five applications per ulcer.

Oasis (Q4102) — Payment is limited to 12 weeks of therapy per ulcer.

TheraSkin (Q4121) — Payment is limited to five applications per ulcer.

DermaCELL® (Novadaq Technologies, Inc., Stryker Global Headquarters, Kalamazoo,

Michigan) (Q4122) — Payment is limited to two applications per ulcer.

Talymed (Q4127) — Payment is limited to five applications per ulcer.

Epifix (Q4131) — Payment is limited to five applications per ulcer.

Dermagraft (Q4106) — Approved for treatment of full-thickness diabetic foot ulcers.

Additionally, diabetic ulcers of the ankle and calf are covered. Frequency is limited to eight

applications per ulcer. Medicare does not cover continued reapplication of Dermagraft for

the same ulcer if satisfactory and reasonable healing progress is not noted after 12 weeks of

therapy.

Kerecis Omega3 Wound® (MariGen® Wound Dressing, Kerecis Limited, Iceland) (Q4158) —

Payment is limited to twelve applications per ulcer.

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GraftJacket (Q4107) — Approved for full-thickness diabetic foot ulcers. Additionally, diabetic

ulcers of the ankle and calf are covered. Payment is limited to one application per ulcer.

Grafix (Q4132 and Q4133) — For the treatment of diabetic foot ulcers and venous leg ulcers

(but not limited to these). Medicare payment for Grafix is limited to five applications per

ulcer.

Alternative covered services:

Physician and surgical visits.

Vacuum-assisted wound closure.

Conservative diabetic foot care.

Conservative venous stasis ulcer wound care.

Compression therapy.

Pneumatic compression.

Standard wound therapy including, but not limited to:

- Assessment of an individual’s vascular status and correction of any amenable

vascular problems.

- Optimization of nutritional status.

- Optimization of glucose control.

- Debridement by any means to remove devitalized tissue.

- Maintenance of a clean, moist wound bed with appropriate dressings.

- Appropriate off-loading.

- Necessary treatment to resolve any infection that may be present.

Background

The extracellular dermal matrix is integral to tissue regeneration and the healing of chronic wounds

(Schultz, 2009). It provides structural support for dermal cells and serves as a reservoir of active

molecules that can be recruited following injury to stimulate cell proliferation and migration. In difficult-

to-heal or chronic wounds, underlying pathophysiological processes (e.g., diabetes or venous

insufficiency) may interrupt the interactions between the extracellular matrix and growth factors that

are necessary for wound healing.

Skin grafts are used to replace damaged or absent areas of dermal tissue associated with disease or

injury (Halim, 2010). They may be full-thickness skin grafts, involving all the layers of the skin, or split-

thickness skin grafts, involving the epidermis and a limited amount of the dermis. Autologous skin grafts,

or autografts, use portions of an individual's own skin and are the least prone to tissue rejection. They

offer excellent material for wound repair, but their use is dependent on the amount of healthy skin

available. Skin harvesting procedures are painful and invasive, and may add stress to an already

compromised individual. Allografts from other human donors or xenografts from another animal species

provide temporary skin that must be replaced with an autograft, but they are susceptible to tissue

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rejection and cross-infection and may conflict with spiritual beliefs.

Skin substitutes:

Skin substitutes (also called tissue-engineered skin substitutes, skin alternatives, and skin

equivalents) contain natural or synthetic matrix scaffolds composed of fibroblast or keratinocyte cells

that provide a mechanically stable framework and tissue infiltration (Halim, 2010). They are

manufactured using selected human cells placed into a matrix with nutrients for the cells to grow into

the desired tissue. Originally developed as an alternative to skin grafts for thermal injury, their use

has been extended to a variety of chronic wounds either to temporarily assume the functions of the

dermal layers until an individual’s own skin repairs itself or a skin replacement is found, or to

permanently replace full-thickness skin. They may reduce infection and promote faster healing to

allow for the beneficial clinical effects associated with complete wound closure (Halim, 2010; Chern,

2009).

The FDA classifies skin substitutes into four main groups (FDA, 2018a, b, and c; Snyder, 2012):

Human- and human/animal-derived skin substitutes regulated through the FDA premarket

approval process or humanitarian device exemption (product code MGR).

Human-derived skin substitutes regulated as human cells, tissues, and cellular and tissue-

based products under 21 CFR 1270 and 1271, and Section 361 of the Public Health Services

Act.

Animal-derived skin substitutes regulated through the FDA 510(k) process (FDA product

code KGN).

Biosynthetic skin substitutes regulated through the FDA pre-market approval and 510(k)

processes.

Searches

AmeriHealth Caritas searched PubMed and the databases of:

UK National Health Services Centre for Reviews and Dissemination.

Agency for Healthcare Research and Quality’s (AHRQ’s) National Guideline

Clearinghouse and other evidence- based practice centers.

The Centers for Medicare & Medicaid Services (CMS).

We conducted searches on February 6, 2018. Search terms were: “skin, artificial” (MeSH), “skin

transplantation" (MeSH), “ulcer” (MeSH), “foot ulcer” (MeSH), “skin ulcer” (MeSH), “leg ulcer”

(MeSH), “diabetic foot” (MeSH), “burns” (MeSH) and free text terms “skin substitutes,” “wound care,”

“apligraf,” “graftskin,” “biobrane,” “dermagraft,” “epifix,” “graftjacket,” “integra,” “marigen,” “orcel,”

“primatrix,” “suprathel,” “theraskin,” and “transcyte.”

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We included:

Systematic reviews, which pool results from multiple studies to achieve larger sample sizes

and greater precision of effect estimation than in smaller primary studies. Systematic

reviews use predetermined transparent methods to minimize bias, effectively treating the

review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies.

Guidelines based on systematic reviews.

Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not

simple cost studies), reporting both costs and outcomes — sometimes referred to as

efficiency studies — which also rank near the top of evidence hierarchies.

Findings

Several skin substitutes have received FDA approval for use in wound care. Many received approval

based on evidence of substantial equivalence to existing products on the market or evidence from low

quality, single-arm studies suggesting acceptable safety and efficacy. Extrapolating data from these

studies to other products and wound types is difficult because of differences in the composition and

healing properties of each product and differences in the etiology and underlying pathophysiology of

chronic wound types (Snyder, 2012). Relatively few of the available skin products have been studied in

randomized controlled trials or other rigorous study designs with sufficient reporting of prior wound

treatments, comorbidities, and patient preferences or outcomes to determine their effectiveness

relative to standard wound care or to each other to make more informed choices in wound care.

For this policy, we considered the highest quality evidence from available randomized controlled trials

(Snyder, 2016; Zelen, 2016; Driver, 2015; Lavery, 2014; Keck, 2012; Schwarze, 2008), systematic reviews

of randomized controlled trials (Santema, 2016; Vloemans, 2016; Jones, 2013; Wasiak, 2013; Snyder,

2012), and evidence-based guidelines (Jones, 2017; Game, 2016; Hingorani, 2016; International Society

for Burn Injury, 2016; Lavery, 2016; Marston, 2016; O'Donnell, 2014; Lipsky, 2012). We also considered

any evidence of a new product called MariGen Wound Dressing. MariGen is a processed piscine (fish)

collagen dermal matrix supplied as a sterile intact or meshed sheet indicated for the management of a

variety of acute and chronic wounds (FDA, 2013). MariGen contains omega-3 polyunsaturated fatty

acids, making it unlikely to invoke an inflammatory response, does not confer a disease risk associated

with other mammalian sources, and contains more bioactive compounds from lower processing

exposure (Magnusson, 2015).

There is sufficient evidence to support using the skin substitutes listed in the Appendix, for treatment of

chronic diabetes foot ulcers, venous stasis ulcers, and burns that fail to respond to several weeks of

standard wound care. Wound healing with these products appears superior to standard wound care

alone in terms of healing time, complete wound closure rate, and complications. The enrolled patients

were of generally good health and free of infected wounds, under good glycemic control, and had

adequate perfusion to the wound area to assist in the healing process. The applicability of these findings

to patients who are in poorer overall health is unclear.

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For diabetic foot ulcers, guidelines uniformly agree that adjuvant therapies, including skin substitutes,

can be considered when the wound has not responded to at least four weeks of standard wound care,

but not as primary treatment options for chronic wounds (Game, 2016; Hingorani, 2016; Lavery, 2016).

For chronic venous ulcers, guidelines recommend skin substitutes in addition to compression therapy in

patients who have failed to show signs of healing after four to six weeks of standard therapy (Marston,

2016; O’Donnell, 2014). The Wound Healing Society recommended skin substitutes using living neonatal

fibroblasts and keratinocytes or porcine matrices based on evidence from randomized controlled trials

finding an increase in the incidence and speed of healing for venous ulcers compared with compression

and a simple dressing alone (Marston, 2016).

Recommendations in burn care rest on the wound condition and product availability (Jones, 2017;

International Society for Burn Injury, 2016). The evidence of the superiority of modern dressings over

conventional dressings is conflicting but suggests that advanced dressings such as skin equivalents can

result in shorter hospital stays and fewer and easier dressing changes, which would enable outpatient

management of wound care in many instances. Amniotic membrane-based products were superior to

most conventional dressings, particularly in areas with scarce blood supply or in whom autologous

grafting is not feasible. The National Pressure Ulcer Advisory Panel (2014) does not recommend skin

substitutes for treatment of chronic pressure ulcers, citing insufficient evidence of effectiveness.

There is insufficient evidence to support the use of other skin substitutes, including MariGen

(Dorweiler, 2017; Yang, 2016), for the treatment of chronic ulcers. Likewise, the evidence is

insufficient to support the use of the skin substitutes listed in the Appendix for treating other types of

chronic wounds. Insufficient evidence does not necessarily imply absence of evidence, only that the

evidence does not meet a rigorous quality threshold. On a case-by-case basis other skin substitutes

may be considered when used in accordance with FDA or manufacturer labeling instructions and can

be justified clinically.

Summary of clinical evidence:

Citation Content, Methods, Recommendations

Dorweiler (2017)

The marine omega-3 wound

matrix (MariGen) for treatment

of complicated wounds

(original text in German with an

English abstract)

Key points:

Case series of 23 patients from three vascular centers with 25 vascular

and/or diabetes mellitus-associated complicated wounds and partially

exposed bony segments were treated with the omega-3 matrix and further

wound management in an outpatient setting where possible.

Location of wounds: thigh (two wounds); distal calf (seven wounds); forefoot

(14 wounds); and hand (two wounds). Time to heal varied between nine and

41 weeks and between 3 and 26 wound matrices were applied per wound.

Authors noted a reduction of analgesics intake with the omega-3 matrix.

Further studies are needed to evaluate the impact of the wound matrix on

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Citation Content, Methods, Recommendations

stimulation of granulation tissue and re-epithelialization as well as the

potential anti-nociceptive and analgesic effects.

Santema (2016)

Cochrane review

Skin grafting and tissue

replacement for diabetic foot

ulcers

Key points:

Systematic review and meta-analysis of 17 randomized controlled trials (1,655

total subjects) with diabetic foot ulcers.

Overall quality: low with a moderate- to high- risk of detection and publication

bias. All but two randomized controlled trials reported industry involvement.

Skin grafts and tissue replacements using Apligraf Graftskin, Dermagraft,

EpiFix, Graftjacket, Hyalograft 3D (Fidia Advanced Biopolymers, Abano

Terme, Italy), Kaloderm® (Tego Science, Seoul, Korea), or OrCel plus

standard care improved healing rate and patient outcome (fewer amputations)

compared with standard care alone.

Insufficient evidence of the relative effectiveness, long term effectiveness, or

cost-effectiveness of different types of skin grafts or tissue replacement

therapies.

Snyder (2016)

A prospective, randomized,

multicenter, controlled

evaluation of the use of

dehydrated amniotic

membrane allograft compared

to standard of care for the

closure of chronic diabetic foot

ulcers

ClinicalTrials.gov Identifier:

NCT02209051

Key points:

A U.S. trial comparing AMNIOEXCEL plus standard care to standard care

alone in 29 adults with type 1 or type 2 diabetes mellitus who have ≥ one

ulcers (Wagner grade 1 or superficial 2 measuring between 1 cm2 and 25 cm2

in area), presenting for > one month with no infection/osteomyelitis; followed

until wound closure or six weeks, whichever occurred first.

Proportion of subjects with complete wound closure (complete re-

epithelialization without drainage or need for dressings) at or before week 6 =

allograft cohort (35%) versus standard of care alone (0%) (intent-to-treat

population, P = 0.017).

Average number of applications per patient = 4.3 ± 1.7 (Mean ± SD), one per

week.

No difference in incidence of treatment-related adverse events, but

adequately powered, comparative studies are needed.

Yang (2016)

A prospective, post-market,

compassionate clinical

evaluation of a novel acellular

fish-skin graft which contains

omega-3 fatty acids for the

closure of hard-to-heal lower

extremity chronic ulcers

Key points:

Case series of 20 patients with 20 full-thickness wounds > 20 cm2 or had

been present for at least 52 weeks. Eighteen patients completed the study.

Study powered to provide evidence of a ≥ 20% wound area reduction over

the first five weeks of therapy.

Fish skin applied with secondary dressing for five sequential weeks, followed

by three weeks of standard wound care. Wound area, skin assessments, and

pain were assessed weekly.

There were a 40% decrease in wound surface area (P < 0.05) and a 48%

decrease in wound depth dressing (P < 0.05). Three of 18 patients had

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Citation Content, Methods, Recommendations

complete closure by the end of the study.

Zelen (2016)

Treatment of chronic diabetic

lower extremity ulcers with

advanced therapies: a

prospective, randomized,

controlled, multi-center

comparative study examining

clinical efficacy and cost

Key points:

Comparison of time-to-heal within 12 weeks in 100 patients with chronic lower

extremity diabetic ulcers treated with weekly applications of Apligraf (n = 33),

EpiFix (n = 32), or standard wound care (n = 35) with collagen-alginate

dressing as controls.

EpiFix was associated with: a significantly higher proportion of wounds

achieving complete closure, probability of wound healing, and likelihood of

healing; and a lower mean time-to-heal than Apligraf or standard wound care.

Median number of grafts used per healed wound = Apligraf 6 (range 1 to 13)

versus EpiFix 2.5 (range 1 to 12).

Median graft cost per healed wound = Apligraf $8,918 (range $1,486 to

$19,323) versus EpiFix $1,517 (range $434 to $25,710) (P < 0.0001).

Driver (2015)

A clinical trial of Integra

Template for diabetic foot ulcer

treatment

Clinicaltrials.gov identifier:

NCT01060670.

Key points:

A multicenter (32 sites), randomized, controlled, parallel group clinical trial

under an Investigational Device Exemption evaluated the safety and efficacy

of Integra Dermal Regeneration Template in 307 subjects (154 active

treatment, 153 controls) for the treatment of nonhealing diabetic foot ulcers.

After a 14-day run-in phase, patients with less than 30% re-epithelialization of

the study ulcer were randomized into a 16 week treatment phase or until

confirmation of complete wound closure (100% re-epithelialization of the

wound surface). Following the treatment phase, all subjects were followed for

an additional 12 weeks.

Integra treatment decreased the time to complete wound closure, increased

the rate of wound closure, improved components of quality of life, and had

less adverse events compared with standard wound care.

Lavery (2014)

The efficacy and safety of

Grafix for the treatment of

chronic diabetic foot ulcers:

results of a multi-centre,

controlled, randomised,

blinded, clinical trial

Key points:

Ninety-seven adult patients with type I or type II diabetes and an index wound

present between four and 52 weeks and located below the malleoli on plantar

or dorsal surface of the foot and ulcer between 1 and 15 cm2; randomized to

Grafix (50 patients) or standard wound care (47 patients).

Results (Grafix versus standard wound care):

- Proportion of patients who achieved complete wound closure = 62%

versus 21% (P = 0.0001).

- The median time to healing = 42 days versus 69.5 days (P = 0.019).

- Adverse events = 44% versus 66% (P = 0.031).

- Wound-related infections = 18% versus 36.2% (P = 0.044).

- Healed ulcers that remained closed = 82.1% (23 of 28 patients)

versus 70% (7 of 10 patients) (P = 0.419).

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Citation Content, Methods, Recommendations

Vloemans (2014)

Optimal treatment of partial

thickness burns in children

Key points:

In general, membranous dressings like Biobrane (six studies) and amnion

membrane (three studies) performed better than the standard of care on

epithelialization rate, length of hospital stay, and pain.

Inconclusive long-term outcomes (e.g., scar formation).

Low-quality evidence.

Jones (2013)

Skin grafting for venous leg

ulcers

Cochrane review

Key points:

Systematic review of 17 randomized controlled trials (1,034 total participants),

including two trials (345 participants) comparing tissue-engineered skin

(Apligraf or Orcel) in conjunction with a dressing.

Overall quality: moderate or high risk of bias.

Bilayer artificial skin, used in conjunction with compression bandaging,

increases venous ulcer healing compared with a simple dressing plus

compression.

Significantly more ulcers healed when treated with bilayer artificial skin than

with dressings. There was insufficient evidence from the other trials to

determine whether other types of skin grafting increased the healing of venous

ulcers.

Wasiak (2013)

Cochrane review

Superficial and partial thickness

burns

Key points:

Systematic review of ten randomized controlled trials (434 patients) comparing

biosynthetic dressings (Biobrane, Transcyte, or Hydron with twice-daily

application of silver sulphadiazine.

Overall quality: very low to low with moderate- to high-risk of bias.

Biosynthetic dressings are more effective than silver sulphadiazine.

No difference in burn healing between biosynthetic dressings and hydrocolloid

dressings.

Antimicrobial-releasing biosynthetic dressings (Hydron) may heal burns more

quickly than silver sulphadiazine or other agent.

Keck (2012)

The use of Suprathel in deep

dermal burns: first results of a

prospective study

Key points:

Prospective, non-blinded, controlled non-inferiority study comparing Suprathel

to autologous skin grafting in 18 patients (median age 45 years, range: 25 to

83 years) with deep-partial-thickness burns.

Fifteen days after surgery, complete wound closure was present in 44.4%

(8/18) of all areas covered with Suprathel and 88.9% (16/18) with split-

thickness grafts (p = 0.008).

Compared to skin grafts, Suprathel had longer healing times but comparable

results concerning early scar formation.

Suprathel can be used to cover the deep dermal burn wounds to save split-

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Citation Content, Methods, Recommendations

thickness skin grafts and its donor sites for the coverage of full-thickness

burned areas.

Snyder (2012) for the Agency for

Healthcare Research and Quality

Skin substitutes for treating

chronic wounds

Key points:

Systematic review of 18 randomized controlled trials — 12 of diabetic foot

ulcers; six of venous stasis ulcers; one of pressure ulcers.

Overall quality: moderate with low to moderate risk of bias.

Evidence of the efficacy of skin substitutes to alternative wound care

approaches are limited in number, apply mainly to generally healthy patients,

and examine only a small portion of the skin substitute products available in

the United States: Apligraf; Dermagraft; Graftjacket; Hyalograft 3D

autograft/LasersSkin; OASIS; and Talymed® (Marine Polymer Technologies,

Inc., Danvers, Massachusetts).

Schwarze (2008)

Suprathel, a new skin

substitute, in the management

of partial-thickness burn

wounds: results of a clinical

study

Key points:

A prospective, randomized, bicentric, nonblinded, clinical study of 30 patients

(mean age 40.4 years) with second-degree burn injuries. Burn injuries were

randomly selected to be treated with either Omiderm (ITG Laboratories,

Redwood City, California) or Suprathel. Follow up ≥ 12 weeks until complete

re-epithelization.

No significant difference in healing time and re-epithelization between

materials.

Benefits of Suprathel are: significantly lower pain scores (P = 0.0072); smooth

detachment without damaging the re-epithelized wound surface; lower

frequency of dressing changes required; ease of care; and often treatment of

choice among patients.

References

Professional society guidelines/other:

Game FL, Attinger C, Hartemann A, et al. IWGDF guidance on use of interventions to enhance the

healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2016; 32 Suppl 1: 75 – 83. DOI:

10.1002/dmrr.2700.

Hingorani A, LaMuraglia GM, Henke P, et al. The management of diabetic foot: A clinical practice

guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical

Association and the Society for Vascular Medicine. J Vasc Surg. 2016; 63(2 Suppl): 3s – 21s. DOI:

10.1016/j.jvs.2015.10.003.

Interqual 2017 Procedures Criteria. Skin Substitute Craft. McKesson Corporation.

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ISBI Practice Guidelines for Burn Care. Burns. 2016; 42(5): 953 – 1021. 10.1016/j.burns.2016.05.013.

Jones CM, Rothermel AT, Mackay DR. Evidence-Based Medicine: Wound Management. Plast Reconstr

Surg. 2017; 140(1): 201e – 216e. DOI: 10.1097/prs.0000000000003486.

Lavery LA, Davis KE, Berriman SJ, et al. WHS guidelines update: Diabetic foot ulcer treatment guidelines.

Wound Repair Regen. 2016; 24(1): 112 – 126. DOI: 10.1111/wrr.12391.

Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice

guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012; 54(12): e132 –

173. DOI: 10.1093/cid/cis346.

Marston W, Tang J, Kirsner RS, Ennis W. Wound Healing Society 2015 update on guidelines for venous

ulcers. Wound Repair Regen. 2016; 24(1): 136 – 144. DOI: 10.1111/wrr.12394.

O'Donnell TF, Jr., Passman MA, Marston WA, et al. Management of venous leg ulcers: clinical practice

guidelines of the Society for Vascular Surgery (R) and the American Venous Forum. J Vasc Surg. 2014;

60(2 Suppl): 3s – 59s. DOI: 10.1016/j.jvs.2014.04.049.

National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel, Pan Pacific Pressure

Injury Alliance. Treatment of pressure ulcers. In: Prevention and treatment of pressure ulcers: clinical

practice guideline. Washington (DC): National Pressure Ulcer Advisory Panel; 2014. p. 126 – 208. [506

references].

Peer-reviewed references:

21 CFR 1271.

About AMNIOEXCEL®. Dermasciences website. http://www.dermasciences.com/amnioexcel. Accessed

February 14, 2018.

Chern PL, Baum CL, Arpey CJ. Biologic dressings: current applications and limitations in dermatologic

surgery. Dermatol Surg. 2009; 35(6): 891 – 906. DOI: 10.1111/j.1524-4725.2009.01153.x.

Dorweiler B, Trinh, T.T., Dünschede, F. et al. The marine Omega3 wound matrix for treatment of

complicated wounds [Die marine Omega-3-Wundmatrix zur Behandlung komplizierter Wunden].

Gefässchirurgie. 2017; 22(8): 558 – 567. DOI: 10.1007/s00772-017-0333-0

Driver VR, Lavery LA, Reyzelman AM, et al. A clinical trial of Integra Template for diabetic foot ulcer

treatment. Wound Repair Regen. 2015; 23(6): 891 – 900. DOI: 10.1111/wrr.12357.

EpiFix. MiMedx website. http://www.mimedx.com/products#quicktabs-product_tabs=2. Accessed

14

February 12, 2018.

FDA 510(k) Premarket Notification database searched using product code KGN. FDA website.

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm. Accessed February 7, 2018.(a)

FDA. Apligraf (Graftskin) for diabetic foot ulcers. Premarket approval P950032/S016. 2000. FDA website.

http://www.accessdata.fda.gov/cdrh_docs/pdf/P950032S016b.pdf. Accessed February 7, 2018.

FDA. Apligraf (Graftskin) for venous ulcers. Premarket approval P950032. 1998. FDA website.

http://www.accessdata.fda.gov/cdrh_docs/pdf/P950032b.pdf. Accessed February 7, 2018.

FDA. Biobrane.Premarket approval P870069/S001. 1990. FDA website.

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P870069S001. Accessed

February 7, 2018.

FDA. Dermagraft. Premarket approval P000036. 2001. FDA website.

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_template.cfm?id=p000036. Accessed

February 7, 2018.(a)

FDA. Hydron Burn Bandage Manual Application 510(k) approval K781406. 1978. FDA website.

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn_template.cfm?id=k781406. Accessed

February 14, 2018.

FDA. Integra Bilayer Matrix Wound Dressing 510(k) Summary K021792. 2002. FDA website

http://www.accessdata.fda.gov/cdrh_docs/pdf2/k021792.pdf. Accessed February 7, 2018.

FDA. Integra Meshed Bilayer Wound Matrix 510(k) Summary K081635. 2008. FDA website.

http://www.accessdata.fda.gov/cdrh_docs/pdf8/K081635.pdf. Accessed February 7, 2018.

FDA. MariGen Wound Dressing. 510(k) summary. 2013. FDA website.

http://www.accessdata.fda.gov/cdrh_docs/pdf13/K132343.pdf. Accessed February 7, 2018.

FDA. OASIS Wound Matrix 510(k) Summary K061711. 2006. FDA website.

http://www.accessdata.fda.gov/cdrh_docs/pdf6/K061711.pdf. Accessed February 7, 2018.

FDA. Orcel bilayered cellular matrix. Premarket approval P010016. 2001. FDA website.

http://www.accessdata.fda.gov/cdrh_docs/pdf/p010016b.pdf. Accessed February 7, 2018.(b)

FDA. Premarket Approval (PMA) searchable database. FDA website.

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm. Accessed February 16, 2018.(b)

15

FDA. PriMatrix Dermal Repair Scaffold 510(k) Summary K153690. 2016. FDA website.

https://www.accessdata.fda.gov/cdrh_docs/pdf15/K153690.pdf. Accessed February 12, 2018.

FDA. Suprathel 510(k) Summary K090160. 2009. FDA website.

https://www.accessdata.fda.gov/cdrh_docs/pdf9/k090160.pdf. Accessed February 12, 2018.

FDA. Talymed 510(k) Summary 102002. 2010. FDA website.

https://www.accessdata.fda.gov/cdrh_docs/pdf10/K102002.pdf. Accessed February 15, 2018.

FDA. Tissue & Tissue Products. Last updated: February 5, 2018. FDA website.

https://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/default.htm. Accessed February

7, 2018. (c)

FDA. Transcyte. Premarket approval P960007/S001 and S002. 2011. FDA website. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P960007. Accessed February 12, 2018.

Grafix. Certifications & Licenses. Osiris Therapeutics website.

http://www.osiris.com/grafix/certifications/. Accessed February, 14, 2018.

GRAFTJACKET Regenerative Tissue Matrix. Instructions for use. November 2015. Wright Medical

Technology website.

http://www.wright.com/wp-content/uploads/2015/04/GJ_ifu_121P0129m_T6.pdf. Accessed February

12, 2018.

Halim AS, Khoo TL, Mohd Yussof SJ. Biologic and synthetic skin substitutes: An overview. Indian Journal

of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India. 2010; 43(Suppl):

S23 – S28. DOI: 10.4103/0970-0358.70712.

Jones JE, Nelson EA, Al-Hity A. Skin grafting for venous leg ulcers. Cochrane Database Syst Rev. 2013; (1):

CD001737. DOI: 10.1002/14651858.CD001737.pub4.

Keck M, Selig HF, Lumenta DB, et al. The use of Suprathel® in deep dermal burns: first results of a

prospective study. Burns. 2012; 38(3): 388 – 395. DOI: 10.1016/j.burns.2011.09.026.

Lavery LA, Fulmer J, Shebetka KA, et al. The efficacy and safety of Grafix® for the treatment of chronic

diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J.

2014; 11(5): 554 – 560. DOI: 10.1111/iwj.12329.

Magnusson S BB, Kjartansson H, Thorlacius GE, et al. Decellularized Fish Skin: Characteristics that

Support Tissue Repair. The Icelandic Medical Journal. 2015; 101(12): 567 – 573. Available at:

http://www.laeknabladid.is/tolublod/2015/12/nr/5664.

16

Santema TB, Poyck PP, Ubbink DT. Skin grafting and tissue replacement for treating foot ulcers in people

with diabetes. Cochrane Database Syst Rev. 2016; 2: Cd011255. DOI:

10.1002/14651858.CD011255.pub2.

Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing.

Wound Repair Regen. 2009; 17(2): 153 – 162. 10.1111/j.1524-475X.2009.00466.x.

Snyder RJ, Shimozaki K, Tallis A, et al. A Prospective, Randomized, Multicenter, Controlled Evaluation

of the Use of Dehydrated Amniotic Membrane Allograft Compared to Standard of Care for the Closure

of Chronic Diabetic Foot Ulcer. Wounds. 2016; 28(3): 70 – 77. Wounds Research Journal website.

http://www.woundsresearch.com/article/prospective-randomized-multicenter-controlled-evaluation-

use-dehydrated-amniotic-membrane. Accessed February 14, 2018.

Snyder DL, Sullivan N, Schoelles KM. Skin substitutes for treating chronic wounds. Technology

assessment report. Prepared by the ECRI Institute Evidence-based Practice Center under contract to

the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD. (Contract No: HHSA 290-2007-

10063. December 18, 2012.

https://www.ncbi.nlm.nih.gov/books/NBK248353/pdf/Bookshelf_NBK248353.pdf. Accessed February

7, 2018.

Vloemans AF, Hermans MH, van der Wal MB, Liebregts J, Middelkoop E. Optimal treatment of

partial thickness burns in children: a systematic review. Burns. 2014; 40(2): 177 – 190. DOI:

10.1016/j.burns.2013.09.016.

Wasiak J, Cleland H, Campbell F, Spinks A. Dressings for superficial and partial thickness burns. Cochrane

Database Syst Rev. 2013; (3): CD002106. DOI: 10.1002/14651858.CD002106.pub4.

Yang CK, Polanco TO, Lantis JC, 2nd. A Prospective, Postmarket, Compassionate Clinical Evaluation of a

Novel Acellular Fish-skin Graft Which Contains Omega-3 Fatty Acids for the Closure of Hard-to-heal

Lower Extremity Chronic Ulcers. Wounds. 2016; 28(4): 112 – 118. Wound Research Journal website.

http://www.woundsresearch.com/article/prospective-postmarket-compassionate-clinical-evaluation-

novel-acellular-fish-skin-graft. Accessed February 14, 2018.

Zelen CM, Serena TE, Gould L, et al. Treatment of chronic diabetic lower extremity ulcers with advanced

therapies: a prospective, randomised, controlled, multi-centre comparative study examining clinical

efficacy and cost. Int Wound J. 2016 Apr; 13(2): 272 – 282. DOI: 10.1111/iwj.12566.

CMS National Coverage Determinations (NCDs):

NCD 270.5 Porcine Skin and Gradient Pressure Dressings. CMS website. https://www.cms.gov/medicare-

coverage-database/details/ncd-details.aspx?NCDId=139&ver=1. Accessed February 15, 2018.

17

A55375 Application of skin substitute grafts for treatment of DFU and VLU of lower extremities

overpayments resulting from claims processing issue. CMS website. https://www.cms.gov/medicare-

coverage-database/details/article-details.aspx?articleId=55375&ver=2. Accessed February 15, 2018.

A54117 Application of Bioengineered Skin Substitutes to Lower Extremity Chronic Non-Healing Wounds.

CMS website. https://www.cms.gov/medicare-coverage-database/details/article-

details.aspx?articleId=54117&ver=36. Accessed February 15, 2018.

A52930 Jurisdiction F Medicare Part B LCD Notification. CMS website. https://www.cms.gov/medicare-

coverage-database/details/article-details.aspx?articleId=52930&ver=2. Accessed February 15, 2018.

A55389 Application of skin substitute grafts clarification of billing when services are performed in the

hospital outpatient setting. CMS website. https://www.cms.gov/medicare-coverage-

database/details/article-details.aspx?articleId=55389&ver=2. Accessed February 15, 2018.

A55035 Billing Requirements for Application of Skin Substitutes (Part B Services Only). CMS website.

https://www.cms.gov/medicare-coverage-database/details/article-

details.aspx?articleId=55035&ver=13. Accessed February 15, 2018.

A55813 Response to Comments: Application of Skin Substitute Grafts for Treatment of DFU and VLU of

Lower Extremities. CMS website. https://www.cms.gov/medicare-coverage-database/details/article-

details.aspx?articleId=55813&ver=2. Accessed February 15, 2018.

Local Coverage Determinations (LCDs):

L35041 Application of Bioengineered Skin Substitutes to Lower Extremity Chronic Non-Healing Wounds.

CMS website. https://www.cms.gov/medicare-coverage-database/details/lcd-

details.aspx?LCDId=35041&ver=62. Accessed February 15, 2018.

L36377 Application of Skin Substitute Grafts for Treatment of DFU and VLU of Lower Extremities. CMS

website. https://www.cms.gov/medicare-coverage-database/details/lcd-

details.aspx?LCDId=36377&ver=2. Accessed February 15, 2018.

L36466 Application of Skin Substitutes. CMS website. https://www.cms.gov/medicare-coverage-

database/details/lcd-details.aspx?LCDId=36466&ver=29. Accessed February 15, 2018.

L34285 Surgery: Bioengineered Skin Substitutes (BSS) for the Treatment of Diabetic and Venous Stasis

Ulcers of the Lower Extremities. CMS website. https://www.cms.gov/medicare-coverage-

database/details/lcd-details.aspx?LCDId=34285&ver=50. Accessed February 15, 2018.

L36690 Wound Application of Cellular and/or Tissue Based Products (CTPs), Lower Extremities. CMS

18

website. https://www.cms.gov/medicare-coverage-database/details/lcd-

details.aspx?LCDId=36690&ver=10. Accessed February 15, 2018.

Commonly submitted codes

Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is

not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and

bill accordingly.

CPT Code Description Comment

15271 Application of skin substitute graft to trunk, arms, legs, total wound surface area

up to 100 sq. cm; first 25 sq. cm or less wound surface area

+15272

Application of skin substitute graft to trunk, arms, legs, total wound surface area

up to 100 sq. cm; each additional 25 sq. cm wound surface area, or part thereof

(List separately in addition to code for primary procedure)

15273

Application of skin substitute graft to trunk, arms, legs, total wound surface area

greater than or equal to 100 sq. cm; first 100 sq. cm wound surface area, or 1%

of body area of infants and children

+15

Application of skin substitute graft to trunk, arms, legs, total wound surface area

greater than or equal to 100 sq. cm; each additional 100 sq. cm wound surface

area, or part thereof, or each additional 1% of body area of infants and children,

or part thereof (List separately in addition to code for primary procedure)

15275

Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears,

orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up

to 100 sq. cm; first 25 sq. cm or less wound surface area

+15276

Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears,

orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up

to 100 sq. cm; each additional 25 sq. cm wound surface area, or part thereof

(List separately in addition to code for primary procedure)

15277

Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears,

orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area

greater than or equal to 100 sq. cm; first 100 sq. cm wound surface area, or 1%

of body area of infants and children

+15278

Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears,

orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area

greater than or equal to 100 sq. cm; each additional 100 sq. cm wound surface

area, or part thereof, or each additional 1% of body area of infants and children,

or part thereof (List separately in addition to code for primary procedure)

ICD-10 Code Description Comment

E08.621 Diabetes mellitus due to underlying condition with foot ulcer

E08.622 Diabetes mellitus due to underlying condition with other skin ulcer

E09.621 Drug or chemical induced diabetes mellitus with foot ulcer

E09.622 Drug or chemical induced diabetes mellitus with other skin ulcer

E10.621 Type 1 diabetes mellitus with foot ulcer

E10.622 Type 1 diabetes mellitus with other skin ulcer

19

ICD-10 Code Description Comment

E11.621 Type 2 diabetes mellitus with foot ulcer

E11.622 Type 2 diabetes mellitus with other skin ulcer

E13.621 Other specified diabetes mellitus with foot ulcer

E13.622 Other specified diabetes mellitus with other skin ulcer

I83.001 Varicose veins of unspecified lower extremity with ulcer of thigh

I83.002 Varicose veins of unspecified lower extremity with ulcer of calf

I83.003 Varicose veins of unspecified lower extremity with ulcer of ankle

I83.004 Varicose veins of unspecified lower extremity with ulcer of heel and midfoot

I83.005 Varicose veins of unspecified lower extremity with ulcer other part of foot

I83.008 Varicose veins of unspecified lower extremity with ulcer other part of lower leg

I83.009 Varicose veins of unspecified lower extremity with ulcer of unspecified site

I83.011 Varicose veins of right lower extremity with ulcer of thigh

I83.012 Varicose veins of right lower extremity with ulcer of calf

I83.013 Varicose veins of right lower extremity with ulcer of ankle

I83.014 Varicose veins of right lower extremity with ulcer of heel and midfoot

I83.015 Varicose veins of right lower extremity with ulcer other part of foot

I83.018 Varicose veins of right lower extremity with ulcer other part of lower leg

I83.019 Varicose veins of right lower extremity with ulcer of unspecified site

I83.021 Varicose veins of left lower extremity with ulcer of thigh

I83.022 Varicose veins of left lower extremity with ulcer of calf

I83.023 Varicose veins of left lower extremity with ulcer of ankle

I83.024 Varicose veins of left lower extremity with ulcer of heel and midfoot

I83.025 Varicose veins of left lower extremity with ulcer other part of foot

I83.028 Varicose veins of left lower extremity with ulcer other part of lower leg

I83.029 Varicose veins of left lower extremity with ulcer of unspecified site

I83.201 Varicose veins of unspecified lower extremity with both ulcer of thigh and

inflammation

I83.202 Varicose veins of unspecified lower extremity with both ulcer of calf and

inflammation

I83.203 Varicose veins of unspecified lower extremity with both ulcer of ankle and

inflammation

I83.204 Varicose veins of unspecified lower extremity with both ulcer of heel and midfoot

and inflammation

I83.205 Varicose veins of unspecified lower extremity with both ulcer other part of foot

and inflammation

I83.208 Varicose veins of unspecified lower extremity with both ulcer of other part of

lower extremity and inflammation

I83.209 Varicose veins of unspecified lower extremity with both ulcer of unspecified site

and inflammation

I83.211 Varicose veins of right lower extremity with both ulcer of thigh and inflammation

I83.212 Varicose veins of right lower extremity with both ulcer of calf and inflammation

I83.213 Varicose veins of right lower extremity with both ulcer of ankle and inflammation

I83.214 Varicose veins of right lower extremity with both ulcer of heel and midfoot and

inflammation

I83.215 Varicose veins of right lower extremity with both ulcer other part of foot and

inflammation

20

ICD-10 Code Description Comment

I83.218 Varicose veins of right lower extremity with both ulcer of other part of lower

extremity and inflammation

I83.219 Varicose veins of right lower extremity with both ulcer of unspecified site and

inflammation

I83.221 Varicose veins of left lower extremity with both ulcer of thigh and inflammation

I83.222 Varicose veins of left lower extremity with both ulcer of calf and inflammation

I83.223 Varicose veins of left lower extremity with both ulcer of ankle and inflammation

I83.224 Varicose veins of left lower extremity with both ulcer of heel and midfoot and

inflammation

I83.225 Varicose veins of left lower extremity with both ulcer other part of foot and

inflammation

I83.228 Varicose veins of left lower extremity with both ulcer of other part of lower

extremity and inflammation

I83.229 Varicose veins of left lower extremity with both ulcer of unspecified site and

inflammation

L97.401 Non-pressure chronic ulcer of unspecified heel and midfoot limited to breakdown

of skin

L97.402 Non-pressure chronic ulcer of unspecified heel and midfoot with fat layer

exposed

L97.403 Non-pressure chronic ulcer of unspecified heel and midfoot with necrosis of

muscle

L97.404 Non-pressure chronic ulcer of unspecified heel and midfoot with necrosis of bone

L97.409 Non-pressure chronic ulcer of unspecified heel and midfoot with unspecified

severity

L97.411 Non-pressure chronic ulcer of right heel and midfoot limited to breakdown of skin

L97.412 Non-pressure chronic ulcer of right heel and midfoot with fat layer exposed

L97.413 Non-pressure chronic ulcer of right heel and midfoot with necrosis of muscle

L97.414 Non-pressure chronic ulcer of right heel and midfoot with necrosis of bone

L97.419 Non-pressure chronic ulcer of right heel and midfoot with unspecified severity

L97.421 Non-pressure chronic ulcer of left heel and midfoot limited to breakdown of skin

L97.422 Non-pressure chronic ulcer of left heel and midfoot with fat layer exposed

L97.423 Non-pressure chronic ulcer of left heel and midfoot with necrosis of muscle

L97.424 Non-pressure chronic ulcer of left heel and midfoot with necrosis of bone

L97.429 Non-pressure chronic ulcer of left heel and midfoot with unspecified severity

L97.501 Non-pressure chronic ulcer of other part of unspecified foot limited to breakdown

of skin

L97.502 Non-pressure chronic ulcer of other part of unspecified foot with fat layer

exposed

L97.503 Non-pressure chronic ulcer of other part of unspecified foot with necrosis of

muscle

L97.504 Non-pressure chronic ulcer of other part of unspecified foot with necrosis of bone

L97.509 Non-pressure chronic ulcer of other part of unspecified foot with unspecified

severity

L97.511 Non-pressure chronic ulcer of other part of right foot limited to breakdown of skin

L97.512 Non-pressure chronic ulcer of other part of right foot with fat layer exposed

L97.513 Non-pressure chronic ulcer of other part of right foot with necrosis of muscle

21

ICD-10 Code Description Comment

L97.514 Non-pressure chronic ulcer of other part of right foot with necrosis of bone

L97.519 Non-pressure chronic ulcer of other part of right foot with unspecified severity

L97.521 Non-pressure chronic ulcer of other part of left foot limited to breakdown of skin

L97.522 Non-pressure chronic ulcer of other part of left foot with fat layer exposed

L97.523 Non-pressure chronic ulcer of other part of left foot with necrosis of muscle

L97.524 Non-pressure chronic ulcer of other part of left foot with necrosis of bone

L97.529 Non-pressure chronic ulcer of other part of left foot with unspecified severity

L97.801 Non-pressure chronic ulcer of other part of unspecified lower leg limited to

breakdown of skin

L97.802 Non-pressure chronic ulcer of other part of unspecified lower leg with fat layer

exposed

L97.803 Non-pressure chronic ulcer of other part of unspecified lower leg with necrosis of

muscle

L97.804 Non-pressure chronic ulcer of other part of unspecified lower leg with necrosis of

bone

L97.809 Non-pressure chronic ulcer of other part of unspecified lower leg with unspecified

severity

L97.811 Non-pressure chronic ulcer of other part of right lower leg limited to breakdown of

skin

L97.812 Non-pressure chronic ulcer of other part of right lower leg with fat layer exposed

L97.813 Non-pressure chronic ulcer of other part of right lower leg with necrosis of muscle

L97.814 Non-pressure chronic ulcer of other part of right lower leg with necrosis of bone

L97.819 Non-pressure chronic ulcer of other part of right lower leg with unspecified

severity

L97.821 Non-pressure chronic ulcer of other part of left lower leg limited to breakdown of

skin

L97.822 Non-pressure chronic ulcer of other part of left lower leg with fat layer exposed

L97.823 Non-pressure chronic ulcer of other part of left lower leg with necrosis of muscle

L97.824 Non-pressure chronic ulcer of other part of left lower leg with necrosis of bone

L97.829 Non-pressure chronic ulcer of other part of left lower leg with unspecified severity

HCPCS Level II Code

Description Comment

Q4101 Skin substitute, Apligraf, per square centimeter Q4102 Skin substitute, Oasis wound matrix, per square centimeter Q4106 Skin substitute, Dermagraft, per square centimeter Q4107 GraftJacket, per square centimeter Q4110 Skin substitute, PriMatrix, per square centimeter Q4121 TheraSkin, per square centimeter

Q4105 Integra, dermal regeneration template DRT or Integra Omnigraft dermal regeneration matrix, per sq cm

22

Appendix.

Medically necessary skin substitutes and clinical indications.

Product Diabetic foot

ulcers

Venous

stasis

ulcers

Thermal

burns Other indications/Additional information

AMNIOEXCEL (Dermasciences, 2018; Snyder, 2016) Dehydrated human amnion/chorion membrane

Apligraf (Jones, 2013; Snyder,

2012; FDA, 2000; FDA, 1998)

Bilayer of human cells and bovine

collagen lattice

The safety and effectiveness of Apligraf have not been established for patients receiving more than five applications.

Biobrane (Vloemans (2014;

Wasiak, 2013; FDA, 1990)

Biosynthetic dressing

For pediatric members with noninfected partial thickness burns < 25 percent of body surface area.

Dermagraft (FDA, 2001a)

Human fibroblast-derived

EpiFix (21 CFR 1271.3[d];

Santema, 2016)

Dehydrated human amnion/chorion

membrane

Additional applications at a minimum of 1-week intervals, for up to a maximum of four in 12 weeks when evidence of wound healing is present (e.g., signs of epithelialization and reduction in ulcer size).

Additional applications beyond 12 weeks are not considered medically necessary regardless of wound status.

Grafix (Osiris Therapeutics, 2018; Lavery, 2014 Dehydrated human amnion/chorion membrane

23

Product Diabetic foot

ulcers

Venous

stasis

ulcers

Thermal

burns Other indications/Additional information

GRAFTJACKET Regenerative

Tissue Matrix (21 CFR 1271;

Santema, 2016; Wright Medical

Technology, 2015)

Human cadaveric donor

Hydron burn bandage (Wasiak, 2013; FDA, 1978) Antimicrobial-releasing biosynthetic dressing

Superficial and partial thickness burns.

Integra Bilayer Matrix (Driver,

2015; FDA, 2008; FDA, 2002)

Bovine collagen

Insufficient evidence from randomized controlled trials for other FDA-approved indications:

Pressure ulcers.

Surgical wounds (donor sites/grafts, post Mohs surgery, post laser surgery, podiatric, wound dehiscence).

Trauma wounds (abrasions, lacerations, second-degree burns and skin tears).

Draining wounds.

OASIS Wound Matrix (Snyder,

2012; FDA, 2006)

Animal-derived extracellular matrix

Insufficient evidence from randomized controlled trials for other FDA-approved indications:

Pressure ulcers.

Chronic vascular ulcers.

Tunneled/undermined wounds.

Surgical wounds (donor sites/grafts, post-Moh's surgery, post-laser surgery, podiatric, wound dehiscence).

Trauma wounds (abrasions, lacerations, second-degree burns, and skin tears).

Draining wounds.

Orcel (Santema, 2016; Jones,

2013; FDA, 2001b)

Human allogeneic cells and bovine

collagen-based

For fresh, clean, split-thickness donor site burn wounds, 10 percent to 80 percent total body surface area, with anticipated life expectancy of six weeks or longer.

Dystrophic epidermolysis bullosa—to close and heal wounds created by hand reconstruction surgery, including those at donor sites.

24

Product Diabetic foot

ulcers

Venous

stasis

ulcers

Thermal

burns Other indications/Additional information

Suprathel Wound and Burn

Dressing (FDA, 2009)

Tri-polymer, bioresorbable dermal

covering

Insufficient evidence from randomized controlled trials for other FDA-approved indications.

Talymed (Snyder, 2012; FDA, 2010) Biosynthetic poly-N-acetyl glucosamine, isolated from microalgae

Insufficient evidence from randomized controlled trials for other approved indications:

Pressure wounds

Ulcers caused by mixed vascular etiologies

Full thickness and partial thickness wounds

Second degree burns

Surgical wounds-donor sites/grafts, post-Mohr’s surgery, post-laser surgery, other bleeding surface wounds, and dehisced wounds.

Abrasions, lacerations.

Traumatic wounds healing by secondary intention.

Chronic vascular ulcers.

Transcyte (formerly Dermagraft-

TC) (Wasiak, 2013; FDA, 2011)

Human fibroblast-derived

Temporary wound covering for surgically excised full-thickness and deep partial-thickness thermal burn wounds before autograft placement.

Mid-dermal to indeterminate depth burn wounds that typically require debridement and may be expected to heal without autografting.