Michelle Kho, PT, PhDon behalf of the CYCLE Investigators

April 23, 2017

Using activity to address frailty:E-CYCLE In-bed cycling

khome@mcmaster.ca

Acknowledgements• Funding

– Canadian Frailty Network– Canada Research Chairs– Canada Foundation for Innovation– Ontario Research Fund Research Infrastructure

Program– Canadian Respiratory Research Network Emerging

Research Leaders Initiative– Ontario Thoracic Society– Canadian Institutes for Health Research

• Equipment loan– Restorative Therapies for bike loans at Toronto

General Hospital and London Health Sciences

Presentation Outline

1. Understand the effects of critical illness on the elderly

2. Describe how activity can address frailty in the critically ill elderly

3. Describe how E-CYCLE addresses frailty in the critically ill elderly

1. WHAT ARE THE EFFECTS OF CRITICAL ILLNESS ON THE ELDERLY?

• Elderly receiving more life support interventions• Mechanical

ventilation• Vasopressors• Renal

replacement• Improved survival

LeRolle et al., Crit Care Med 2010;38(1):59-64.

Brummel et al., Crit Care Med. 2015; 43:1265–1275.

Disability < 3 months > 6 months

Mobility 14% - 87%

Activities of daily living (prevalence) 33% - 58% 12% - 97%

Instrumental activities of daily living 22% - 45%

Cognitive impairment 56%

Disability is common in elderly who survive critical care

Towards RECOVER:Prospective 1-year follow-up of 391 ICU survivors

Clinical

Course

ICU

Discharge

ICU

Admission

Setting: 10 Canadian medical-surgical ICUsPopulation: Adult ICU survivors MV >=7 d

Outcomes:• Functional Independence Measure (FIM)• Impact of Event Scale (PTSD)• Beck Depression Inventory

7 days 3 months 6 months 12 months

Herridge et al, AJRCCM. 2016. In press. Available online March 2016.

• Hip & shoulder girdle weakness; poor coordination, gait, & balance• 40% able to walk @ 7 days post-ICU

• ~ 1 in 5 reported important symptoms of PTSD• ~ 1 in 5 reported moderate to severe depressive symptoms

Median (IQR) ICU LOS: 16 (11-27); Hospital LOS: 49

Herridge et al, AJRCCM. 2016. In press. Available online March 2016.

FIM Score 126 >60 50 <40 18

Totally independent

Modified Independence

ModerateAssistance

Max to Total Assistance

Totally dependent

• ICU LOS and age predicted FIM @ 7 days

• FIM @ 7 days predicted 1 year recovery

No impact of Admission Dxor APACHE II score

2. HOW CAN ACTIVITY ADDRESS FRAILTY IN THE CRITICALLY ILL ELDERLY?

Continuum of physical activity

Bedrest Completely Passive

Completely Active

Increasing physical activity and patient engagement in rehab

What is Sedentary Behaviour?

• Any waking sitting or lying behaviour with low energy expenditure

– <1.5 metabolic equivalents (METs)1

• Emerging science in exercise physiology

– New MESH term 20102

• Different from physiology of exercise

• NOT absence of meeting physical activity guidelines

1Appl Physiol Nutr Metab. 2012. 37: 540-42.2Diabetologica. 2012. 55:2895-2905.

Continuum of physical activity

https://sites.google.com/site/compendiumofphysicalactivities/

1.0

Sleeping

1.5

Sitting

< 1.5 METS

2.0Grooming

2.5Dressing

9.8Running

60 min

10K

10.0Hockey

Soccer

3.5Descending

stairs

8.0Synchro

Swimming

23.0Running

27 min

10K

> 1.5 METS

Dunstan et al., European Endocrinology. 2010. 6(1):19-23.

3. HOW DOES E-CYCLE ADDRESS FRAILTY IN THE CRITICALLY ILL ELDERLY?

Some considerations……

• Is it feasible to conduct early rehabilitation with critically ill, elderly patients?

• Few rehabilitation studies in critically ill, elderly patients

• Elderly patients underrepresented in critical care clinical trials1

1Cooke et al., Crit Care Med 2010;38(6):1450-1457.

Rationale for E-CYCLE

• RCT: PT and OT started within 1.5 days of intubation improves independence at hospital discharge

– Main difference: 19.2 minutes/ day during MV

• RCT: In-bed cycling started ICU day 14 improved 6-minute walk test distance at hospital discharge

• Question: Can we initiate in-bed cycling with patients earlier in their ICU stay, and will it improve patient outcomes?

Crit Care Med. 2009. 37(9): 2499-2505.

Lancet. 2009. 373: 1874-1882.

CYCLE: Critical Care Cycling to Improve Lower Extremity Strength

Research Question:In medical-surgical ICU patients, does 30 minutes of in-bed cycling and routine PT started within the first 4 days of mechanical ventilation, compared to routine PT improve patient function at hospital discharge?

CYCLE: Critical Care Cycling to Improve Lower Extremity Strength

CYCLEPreparation phase

Survey development: pt, family, clinician satisfaction with rehabilitation

Retrospective chart

audit ✔ JCC 2015

CYCLE-R

Systematic Review

Uni-CYCLE

ICAN Rehab

TryCYCLE:Phase II open label study

1 center, 33 pt prospective cohort•Design the intervention; select outcomes; assess fidelity, safety, satisfaction, and acceptability ✔PLoS One 2016

CYCLE RCT:Phase III randomized trial

Multicenter RCT

BICYCLE

BehaviouralIntervention for Knowledge Translation

CYCLE$

Economic evaluation

7 center, 66 pt pilot RCT• Feasibility✔ BMJ Open 2016 (protocol paper)

CYCLE RCT:Phase II pilot randomized trial

CYCLE Research Program Philosophy

• Integrated knowledge translation approach

• Incremental and systematic

– Safety & Feasibility

• Consent, intervention delivery, outcome measures

– Scalability among other centres

• Pilot RCT before full RCT

• In collaboration with the Canadian Critical Care Trials Group

Example of in-bed cycling

CYCLE inclusion criteria

• Adult patient ≥ 18 years old

• Invasively mechanically ventilated ≤ 4 days

• Expected additional 2 day ICU stay

• Walked independently pre-hospital

• ICU length of stay ≤ 7 days

Awake

Outcomes #1 (short)

RCT Study Schema

30 min cycling + Routine PT or Routine PT

Clinical Course

Study Outcome Assessments

ICU Admission

Routine PT

Study Entry ≤4 d MV

Intubated

ICU Discharge

Outcomes #2

Hospital Discharge

Outcomes #3

• Intervention delivered by front-line physiotherapists in 7 Canadian centers• Randomized intervention 5d/ wk until ICU d/c or 28 days• Cycling patients -> d/c cycling if patient can march on the spot x 2 days

Trial Registration: NCT02377830

RESEARCH QUESTION:

In medical-surgical ICU patients, is it safe and feasibleto initiate 30 minutes of in-bed leg cycling within 4 days of starting mechanical ventilation and through the ICU stay?

PLoS One. 2016;11(12):e0167561.

TryCYCLE - Patients’ Cycling DistancesMedian 5 (3, 8) sessions/ patient

Per session, km 1.0 (0.9, 2.0)

Per patient, km 8.7 (5.0, 14.0)

0

5

10

15

20

25

30

35

40

45

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

Total Distance(Km)

Age ≥ 65

Age ≤ 65

RESEARCH QUESTION:

Is it feasible to enroll newly mechanically ventilated elderly adults in a multi-centre pilot RCT of early in-bed cycling plus routine physiotherapy versus routine physiotherapy alone to inform a larger RCT?

E-CYCLE Pilot RCT Feasibility Outcomes

1. Accrual: Following orientation, the overall average accrual rate will be 3 pts/ month (1 pt/month/ site)

2. Protocol violations: The cycling protocol can be implemented with <20% protocol violations

3. Outcome Measures: >80% of outcomes will be measured as scheduled

4. Blinded Outcome Assessment: >80% of outcomes at hospital discharge will be assessed by personnel blinded to group allocation

PRELIMINARY RESULTS

Patients Enrolled Over Time66

0

10

20

30

40

50

60

70

# o

f P

atie

nts

Month

Monthly Total

Overall

As of June 23rd, 2016

20162015

JCC & HGH

TGH

SMH

SJH

OGH & LHS

SJH= St Joseph’s HospitalJCC= Juravinski Cancer CentreHGH= Hamilton General HospitalTGH= Toronto General HospitalSMH= St. Michael’s HospitalOGH= Ottawa General HospitalLHS= London Health Sciences

66

0

10

20

30

40

50

60

70

SJH JCC HGH TGH SMH OGH LHS

# o

f P

atie

nts

Site

≥ 65 yrs

< 65 yrs

Cumulative Totals

Patients Enrolled by Site and Age

SJH= St Joseph’s HospitalJCC= Juravinski Cancer CentreHGH= Hamilton General HospitalTGH= Toronto General HospitalSMH= St. Michael’s HospitalOGH= Ottawa General HospitalLHS= London Health Sciences

As of June 23rd, 2016

Screening Milestone Total

Patients screened 867

Patients excluded 605

Patients eligible 263

Patients eligible not randomized 197

Total number of patients enrolled 66

Overall Screening Synopsis

Data as of June 23rd; Analysis as of August 26th, 2016

77% of eligible

patients are not

randomized

Overall Screening- Reasons Eligible Not Randomized

12

0 50 100

PT resources- CYCLE pts

PT resources- Study on Hold

Other

No PT available

PT resources- No CYCLE pts

Patient or SDM declines consent

Unable to consent/no SDM

Previously enrolled

No RC available

Physician declines consent

# of Patients (n = 197)Reason

Overall Consent Rate = 85%

Data as of June 23rd, 2016Analysis as of August 26th, 2016

E-CYCLE Consent Rate = 82.5%

Overall Screening- Reasons Eligible Not Randomized

91

29

15

14

0 50 100

PT resources- CYCLE pts

PT resources- Study on Hold

Other

No PT available

PT resources- No CYCLE pts

Patient or SDM declines consent

Unable to consent/no SDM

Previously enrolled

No RC available

Physician declines consent

# of Patients (n = 197)Reason

57% of all eligible patients are not

randomized due to PT resources

35% of ENR due to CYCLE patients on

study

Data as of June 23rd, 2016Analysis as of August 26th, 2016

Characteristics of included patientsE-CYCLE

Characteristic N = 33 patients

Female, n (%) 12 (36.4%)

Age, mean (SD) years 74.6 (7.4)

APACHE II Score, mean (SD) 25.8 (8.0)

Medical admission diagnosis, n (%) 27 (81.8%)

ICU length of stay, median [IQR], days 11.0 [9 – 23]

Hospital length of stay, median [IQR], days 25 [18 – 36]

ICU mortality, n (%) 10 (30.3%)

Hospital mortality, n (%) 11 (33.3%)

Characteristics of included patientsE-CYCLE

Characteristic N = 33 patients

Female, n (%) 12 (36.4%)

Age, mean (SD) years 74.6 (7.4)

APACHE II Score, mean (SD) 25.8 (8.0)

Medical admission diagnosis, n (%) 27 (81.8%)

ICU length of stay, median [IQR], days 11.0 [9 – 23]

Hospital length of stay, median [IQR], days 25 [18 – 36]

ICU mortality, n (%) 10 (30.3%)

Hospital mortality, n (%) 11 (33.3%)

CYCLE Pilot RCT Feasibility Outcomes

R

Early cycling + routine PTN=36

Routine PTN=30

7 Medical/ Surgical ICUs

N=66

79.2% (146/185)

86.4% (38/44)

81.6% (31/38)

2. Cycling delivery >80%

3. PFIT-s hospital d/c>80%

4. PFIT-s blinded>80%

• 2/36 patients did not receive any cycling• Median [IQR] 3 [2 to 5] days from ICU admit to 1st bike• 1/146 cycling sessions stopped due to persistent

tachycardiaPreliminary data.

Future Opportunities for E-CYCLE• Clinical:

– Physiotherapist capacity to provide intervention

• Program management vs. department-based models

– CYCLE Vanguard

• Optimize trial design & involvement of clinical PTs

– Equipment infrastructure, clinician education

• Patient-centred: Who benefits most?

• Interdisciplinary: Cycling is one tool

• Scaling: International collaborators

But the biggest question was: could we do this research study? Our staffing was changing as people were going on maternity leaves and others coming back. The ICU was busy, and there were other demands on our time. Setting up a machine and running it for half an hour, then taking it down seemed like it would take over our day.

https://physiotherapy.ca/blog/early-bed-cycling-icu-perspectives-frontline-pt

We were able to do it because we learned to be a stronger physiotherapy team.

Presentation Outline

1. Understand the effects of critical illness on the elderly

2. Describe how activity can address frailty in the critically ill elderly

3. Describe how E-CYCLE addresses frailty in the critically ill elderly

Parting thought:• How can we

meaningfully engage frontline healthcare providers and hospital decision makers in critical care research for frail Canadians?

khome@mcmaster.ca

Investigators (Alphabetical)• Dr. Ian Ball, Western• Dr. Karen Burns, St. Mike’s• Dr. Deborah Cook, McMaster/ SJH (mentor)• Dr. Alison Fox-Robichaud, McMaster/ Hamilton

General• Dr. Jan Friedrich, St. Mike’s• Dr. Margaret Herridge, Toronto General• Dr. Tim Karachi, McMaster/ Juravinski• Dr. Karen Koo, Western/ Swedish Healthcare• Mr. Vince Lo, Toronto General• Dr. Sunita Mathur, Toronto General/ U Toronto• Dr. Marina Mourtzakis, U Waterloo• Dr. Joe Pellizzari, McMaster/ SJH• Mr. Tom Piraino, McMaster/ SJH• Dr. Bram Rochwerg, McMaster, Juravinski• Dr. Jill Rudkowski, McMaster/ SJH• Dr. Andrew Seely, U Ottawa/ Ottawa General• Dr. Jean-Eric Tarride, McMaster

Methods Centre (Hamilton, ON)• Ms. France Clarke, McMaster/ SJH• Dr. Aileen Costigan, SJH• Mr. Alex Molloy, SJH• Ms. Janelle Unger, U Toronto• Ms. Devin McCaskell, U Toronto/ SJH• Mr. Mike Ciancone, McMaster/ SJH

RCT Team Members

Physiotherapists/ Physiotherapist Assistants; RCs; RAsSt. Joseph’s Healthcare: Daana Ajami, Laura Camposilvan, Magda McCaughan, Kristy Obrovac, Christina Murphy, Wendy Perry, Diana Hatzoglou, Miranda Prince, Bashir Versi; RCs France Clarke, Aileen Costigan, Alex Molloy

Hamilton Health Sciences – Juravinski: Leigh Ann Niven, Tania Brittain, Jessica Temesy, Andrea Galli, Chris Farley, Shivaun Davidson, Helen Bishop, Shannon Earl, Chelsea Hale, Gillian Manson; RC Tina Millen

Hamilton Health Sciences – General: Ashley Eves, Annie Newman, Judi Rajczak, Julie Reid, Elise Loreto, Sarah Lohonyai, Jennifer Duley, Sue Mahler, Matt McCaffrey, Jessica Pilon-Bignell; RC Ellen McDonald

Toronto General: Vince Lo, Sunita Mathur, Gary Beauchamp, Anne-Marie Bourgeois, Nathalie Côté, Sherry Harburn, Adriane Lachmaniuk, Megan Hudson, Sophie Mendo, Teresa Torres; RC Andrea Matte; RAs Jaimie Archer, Daniel Chen, Cristian Urrea, Lia Stenyk

London Health Sciences: Kristen Abercombie, Jennifer Curry, Erin Blackwell-Knowles, Tania Larsen, Jennifer Jackson; RC Eileen Campbell; RA Rebecca Rondinelli

St. Michael’s Hospital: Deanna Feltracco, Christine Leger, Sarah Brown, Diana Horobetz, Verity Tulloch, Anna Michalski, Natalia Zapata; RCs Orla Smith, Kurtis Salway, Gyan Sandhu

Ottawa General: Rachel Goard, Josee Lamontagne, Michelle Cummings, Sarah (Sal) Patten; RCs Rebecca Porteous, Heather Langlois, Irene Watpool, Brigette Gomes, Shelley Acres

RCT Team Members