STUDY PROTOCOL Open Access

Effects of a long-term home-based exercisetraining programme using minimalequipment vs. usual care in COPD patients:a study protocol for two multicentrerandomised controlled trials (HOMEX-1 andHOMEX-2 trials)Anja Frei* , Thomas Radtke, Kaba Dalla Lana, Julia Braun, Ramona M. Müller and Milo A. Puhan

Abstract

Background: Exercise training is an important component of pulmonary rehabilitation (PR) programmes in chronicobstructive pulmonary disease (COPD), but the great majority of COPD patients who would benefit from PR neverfollow such programmes or fail to maintain exercise training after PR completion. Against this background, wedeveloped an exercise training programme that requires minimal equipment and can be implemented long-termin the patient’s home-setting. The aims of the HOMEX-1 and HOMEX-2 trials are to assess the effectiveness of thishome-based exercise training programme in two groups of COPD patients over the course of one year: patientswho have completed PR (HOMEX-1 trial) and patients who did not enrol in existing PR programmes within the lasttwo years (HOMEX-2 trial).

Methods: HOMEX-1 and HOMEX-2 are multicentre, parallel group, randomised controlled trials. For both trialseach, it is planned to include 120 study participants with a diagnosis of COPD. Participants will be randomisedwith a 1:1 ratio into the intervention group or the control group (usual care/no intervention). The interventionconsists of minimal-equipment exercise training elements with progressive level of intensity, conducted by theparticipant during six days per week and instructed and coached by a trained health care professional duringthree home visits and regular telephone calls during one year. Primary outcome is change in dyspnoea (domainof Chronic Respiratory Questionnaire) from baseline to 12-months follow-up. Secondary outcomes are change indyspnoea over the course of the year (assessed at 3, 6 and 12 month) and change in functional exercise capacity,physical activity, health-related quality of life, health status, exacerbations and symptoms from baseline to 12months follow-up. In addition, explanatory, safety and cost-effectiveness outcomes will be assessed. We willconduct intention-to-treat analyses separately per trial and per protocol analyses as sensitivity analyses.

Discussion: The HOMEX-1 and HOMEX-2 trials assess a novel intervention that provides an innovative way ofmaking exercise training as accessible as possible for COPD patients. If the intervention proves to be effectivelong-term, it will fill the gap of providing an easily accessible and feasible intervention so that more COPDpatients can follow an exercise programme.

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* Correspondence: anja.frei@uzh.chEpidemiology, Biostatistics and Prevention Institute (EBPI), University ofZurich, Hirschengraben 84, 8001 Zurich, Switzerland

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Frei et al. BMC Pulmonary Medicine (2019) 19:57 https://doi.org/10.1186/s12890-019-0817-7

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Trial registration: ClinicalTrials.gov Identifier: HOMEX-1 NCT03461887 (registration date: March 12, 2018;retrospectively registered); HOMEX-2 NCT03654092 (registration date: August 31, 2018).

Keywords: COPD, Exercise training intervention, Randomised controlled trial, Home-based, Quality of life,Functional exercise capacity, Physical activity, Minimal equipment

BackgroundExercise training is an important component of pul-monary rehabilitation (PR) and the management ofCOPD [1]. Numerous trials have shown that exercisetraining with or without additional PR elements leadsto clinically significant improvements in health-relatedquality of life (HRQoL) and exercise capacity in pa-tients with COPD [2]. However, despite the well-knownbenefits, the great majority of patients who would profitfrom PR never follow such a programme. On the otherhand, for those patients who undergo a supervised ex-ercise training programme, it is often challenging tomaintain exercising after PR completion and to imple-ment the training into the daily life home-setting.Major barriers for not participating or adhering to pro-grammes are travel and transport to the centre, disrup-tion to established routine, lack of perceived benefits,social isolation, inconvenient timing, comorbidities anddepressive symptoms [3–7].Traditionally, PR programmes were given under direct

supervision at a rehabilitation centre with participantsattending as inpatients or outpatients. However, bothcommunity-based and home-based programmes are be-coming increasingly popular [1]. Of the studies includedin the most recent systematic review on the effects ofPR vs. usual care in COPD patients [2], approximatelyone third comprised home-based programmes or pro-grammes that included an element of home-based train-ing embedded in an inpatient or outpatient setting. Ofthe studies that focused on home-based training alone,the programmes typically lasted eight to twelve weeks,the follow-up assessments were primarily conducted atthe end of the programme without a more long-termperspective and their effect on HRQoL and exercise tol-erance compared to usual care was not consistent acrossstudies [8–17].Evidence from two recent trials suggests that the effects

of comprehensive home-based PR programmes wereequivalent or non-inferior to the effects of outpatient PR,both after completion of the programmes (12 and 8weeks,respectively) and after one year [18, 19]. These results weresupported by a current systematic review that found similarbeneficial effects of home-based compared to outpatient ex-ercise training programmes [20]. However, as demonstratedin other studies [1, 21], in both, the home-based and

outpatient PR groups the strong effects detected immedi-ately after completion of PR either decreased [18] or van-ished in the long-term after 12months [19]. Another recenttrial showed beneficial effects of a long-term maintenanceexercise training programme (following PR) after two years;however, the programme included use of cycle ergometerswhich were delivered to the participants’ home, and weighttraining. Moreover, patients visited the hospital for super-vised exercise training sessions on a regular basis [22].Against this background, we developed a novel exercise

training programme that requires only minimal equip-ment and that can be easily implemented in the patient’shome-setting in the long-term (HOMEX intervention).The overall objectives of the HOMEX-1 and HOMEX-2trials are to assess the effectiveness of this intervention intwo groups of COPD patients by means of two rando-mised controlled trials (RCT). The HOMEX-1 trial fo-cuses on patients who completed PR no longer than onemonth ago, aiming at maintaining exercise training effectselicited during PR for the long-term (post PR maintenancegroup). The HOMEX-2 trial focuses on patients who didnot participate in PR within the last two years aiming tooffer a low-threshold complementary option for regularexercise training in their home setting (no PR group). Theprimary objective of the studies is to assess the effect ofthe HOMEX intervention on dyspnoea over the course ofone year; secondary objectives are to evaluate the effect ofthe intervention on functional exercise capacity, physicalactivity, health status, exacerbations and COPD associatedsymptoms. Additional objectives are to explore the pa-tients’ compliance and adherence to the exercise trainingprogramme and to evaluate acceptability, implementationfeasibility and cost-effectiveness of the intervention.

MethodsStudy designHOMEX-1 and HOMEX-2 are multicentre, randomised(ratio 1:1), parallel group, controlled trials (Clinicaltrials.gov Identifier: NCT03461887 and NCT03654092).Study participants are randomly assigned either to thehome-based exercise group (intervention group) or tono intervention/usual care (control group). Both trialswere approved by the local ethics committees (KantonaleEthikkommission Zürich, Ethikkommission Bern,Ethikkommission Zentral- und Nordwestschweiz;

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BASEC-Nr. 2017–02092) and are conducted in ac-cordance with the Declaration of Helsinki and theEC/ICH-Guidelines on Good Clinical Practice. Thestudy is restricted to participants who provided writ-ten informed consent.

Study setting, study population and recruitmentFor HOMEX-1, eligible participants are identified from theSwiss inpatient PR centres Klinik Barmelweid, Berner RehaZentrum Heiligenschwendi and Zürcher RehaZentrumWald, and the outpatient PR centre Kantonsspital Winter-thur. All patients admitted to the PR centres will bescreened for study eligibility by the local investigators. Eli-gible patients will be consecutively informed about thestudy and invited to participate. After written informedconsent, baseline assessments will be conducted. Recruit-ment for HOMEX-1 is planned for 12months; the first par-ticipant in the first centre was enrolled by the end ofJanuary 2018.For HOMEX-2, study participants will be primarily re-

cruited in the Canton of Zurich. Potential participants willbe informed about the study by means of informationflyers including a phone number of a contact person ofthe Epidemiology, Biostatistics & Prevention Institute(EBPI), University of Zurich, through direct contact withLUNGE ZURICH staff (local Lung Association of theCanton of Zurich), general practitioners and other healthprofessionals. Additional information on the study is pro-vided in newsletters of LUNGE ZURICH and/or adver-tisements and the EBPI homepage. EBPI study staff willconsecutively conduct screening visits at the EBPI in Zur-ich, where potential participants will be screened for eligi-bility and receive oral and written information. Apulmonologist will confirm COPD diagnosis based on alung function measurement (portable hand-held spirom-etry) and assessment of lifetime smoking and occupationalexposure. In case of any uncertainties regarding COPDdiagnosis, the study team will contact the participants’general practitioner or pulmonologist. After written in-formed consent, baseline assessments will be conducted.Recruitment for HOMEX-2 will start by the end of Sep-tember 2018 and is planned for 12months.

Inclusion criteria

HOMEX-1 and HOMEX-2– Signed informed consent– Diagnosis of COPD, defined as forced expiratory

volume in 1 s/forced vital capacity (FEV1/FVC)ratio < 0.7 and FEV1 < 80% predicted afterbronchodilation, with or without chronic symptoms(cough, sputum production) corresponding toGOLD stages II-IV

– Male and female participants ≥40 years of age

– Knowledge of German language to understand studymaterial and assessments

HOMEX-1 only– Completion of an inpatient or outpatient PR no

longer than 1 months ago

HOMEX-2 only– No participation in an inpatient or outpatient PR

within the last two years

Exclusion criteria

HOMEX-1 and HOMEX-2– Participants not able to conduct the exercise

training programme due to physical, cognitive orsafety reasons, as judged by investigator; e.g., lowerlimb joint surgery within preceding three months,unstable cardiac disease, predominant neurologicallimitations

HOMEX-2 only– Planned participation in a PR programme

Study groupsParticipants assigned to the intervention group will re-ceive the HOMEX intervention (minimal equipmentexercise programme; described below), participantsassigned to the control group will not receive the inter-vention (usual care). Apart from receiving the HOMEXintervention or not, the study does not impact any otherplanned treatments.

Study interventionThe exercise training programme HOMEX was devel-oped by health professionals and experts from the EBPIand thoroughly piloted in several COPD patients bymeans of cognitive debriefing techniques (study mater-ial) and by evaluation of the motivational counsellingstrategy, instruction, conduct and feedback of the exer-cises and optimal scheduling of the home visits andfollow-up calls.To consider the challenge of conducting regular exercise

training in the long-term, we developed the interventionunder consideration of important determinants of healthbehaviour. We therefore aimed to instruct and coach theminimal equipment exercise training programme to par-ticipants based on motivational interviewing techniquesand with support of self-management skills like problemsolving, decision making and action planning. The com-prehensive coaching targets the participant’s behaviour atvarious levels; i.e., the individual level (e.g., personal goalsetting), interpersonal level (e.g., social support) and envir-onmental level (e.g., own flat / house) [23].

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The study intervention consists of three visits at the par-ticipant’s home by a trained health care professional, the“personal coach” (mainly physiotherapists, but also otherprofessions; training and supervision described below), ex-ercise sessions conducted during six days per week, illus-trated by cards, an interactive exercise training book andsupporting telephone calls. Additional intervention ele-ments are that a relative, friend or close person is involvedas a “sparring” partner to support the participant to con-duct the exercise training programme on a regular basisand that the general practitioner is informed about theparticipation of his/her patient in the intervention.

Initial visit at the participant’s homeAt programme onset, the personal coach conducts an ini-tial visit at the patient’s home (approx. 120min). The aimsof this visit are to establish trust and confidence, to ex-plore the participant’s ability to perform exercises and toinstruct him/her for the first part of the exercises and theuse of the exercise cards. Besides the cards, the coach in-troduces the participant also to the daily use of the inter-active training book in order to report individualisedgoals/rewards, record and evaluate daily workouts and de-fine concrete motivational resources. Furthermore, theconcrete training setting at home, i.e., the precise locationof the chair and the training schedule will be determined.The communication based on motivational interviewtechniques aims to ensure a high level of training adher-ence throughout the study. The patient is also instructedto call his coach upon interruptions of training for morethan three consecutive days due to any reason.

Second home visit after three weeksThe aim of the second visit is to further build on trustand confidence, to instruct the participant in theremaining exercise cards, to verify exercise performance,to ensure the regular adaption in training volume andtraining intensity, to check the daily entries in the train-ing book and to discuss and adapt with the participantshort and long term goal attainment.

Third home visit after eight to nine weeksThe aim of the third home visit is to ensure open andhonest communication, the appropriate performance ofall exercises, to check and ensure the regular adaption intraining volume and training intensity, to discuss andmonitor the first short term goal achievement and todiscuss and possibly adapt the long-term goal.

Individualised strength-training programmeThe exercise training consists of three trunk, threeupper limb and four lower limb exercises that can beperformed at three different levels. The exercises will be

performed six days per week for about 15–20 min usinga chair and elastic exercise bands on different resistancelevels. The daily strength training is always introducedby a whole body warm-up and finalised by two or threeappropriate stretching exercises. During the programme,the intensity of exercises will progressively increase. Allexercises are illustrated on 38 attractive exercise cardsincluding possible gain, detailed instructions to verifythe correct performance, training volume and intensity.To document the training progress, the participants willrecord their completed training sessions in their trainingbook which will also be used to monitor trainingadherence.

Regular telephone callsDuring the 12-month exercise training programme thepersonal coaches will regularly call the participants,directed by a guidance manual to motivate the partici-pants, to discuss training progress and concrete benefitsand barriers and to adapt goals and the trainingprogramme (exercise intensity, duration) to the individ-ual needs, if required. During the first ten days, thecoach will call the participant twice, subsequently onceevery two weeks for the first 6 months and every fiveweeks after, except for situations when training elementshave changed. Participants are instructed to call theircoach if they could not perform the exercises for morethan three consecutive days (i.e., except Sundays), theywill then be followed by additional phone calls. To en-sure and guide the training restart, additional phonecalls will be conducted, with similar frequency as afterthe first home visit. Since motivational components area key issue for programme success, the telephone callswill be based on motivational interview techniques andtarget on support in self-management skills to facilitatea high level of training adherence.

Training and supervision of health care professionals(“personal coach”)The health care professionals who will work as personalcoach will be trained by the master coach (KDL, whowas much involved in developing and piloting of theintervention) during a basis and an update training ses-sion. For each participant contact (i.e., all 3 home visitsand the telephone contacts), the coach will be providedwith guidance documents with algorithms how toproceed in specific situations. During the time of theintervention, the coach will be in regular contact withthe study team as well as part of a virtual chat roomwith all other coaches moderated by members of thestudy team and supported by the master coach. Themaster coach will accompany the coach at least once ata home visit to ensure the conduct of the interventionaccording to protocol (fidelity).

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Study outcomesMain study outcomes are assessed during study visits be-fore randomisation at baseline (T0, T1) and at 12-monthsfollow-up (T4). Further assessments are conducted after 3months (T2) and after 6 months (T3). Table 1 displays thestudy visits and assessment of the outcomes.

Primary outcomeThe primary outcome is the change in dyspnoea, measuredby the Chronic Respiratory Questionnaire (CRQ) dyspnoeadomain (standardised version, self-administered) frombaseline until 12-months follow-up [24]. The CRQ dys-pnoea domain is one of the most commonly used dyspnoeainstrument in trials of PR and contains five questionsresponded on a 7-point Likert-type scale ranging from 1(most severe dyspnoea) to 7 (no dyspnoea).

Secondary outcomesSecondary outcomes are assessed at baseline and at12-months follow-up, except for change in CRQ dys-pnoea subscale, which is additionally assessed at 3 and 6months follow-up.

Functional exercise capacityThe Six-Minute Walk Test (6MWT) [25, 26] is a vali-dated and widely used test in COPD patients to assessfunctional exercise capacity. The test will be performedaccording to European Respiratory Society (ERS)/American Thoracic Society (ATS) standards [25, 27].The patients will be instructed to walk as far as possibleduring 6 min and they will receive standardized encour-agements. Two tests will be performed with at least 30min rest in-between and the test with the higher totalwalking distance in meters will be recorded.The 1-Minute Sit-to-Stand Test (1-min STS test) is a

validated test to assess functional exercise capacity inindividuals with COPD [28]. It counts the number ofrepetitions of full sit-to-stand movements from a stand-ard chair (i.e. standing up and sitting down again) thata person completes during one minute. The STS move-ment requires the participant to stand up completelyvertical until in the straight upright position and returnto the sitting position with knees flexed to approxi-mately 90 degrees. Prior to the STS test participantswill practice the STS movement once or twice in orderto familiarise themselves.

Health-related quality of life (HRQoL)HRQoL will be assessed by the CRQ domains fatigue,emotional function and mastery [24]. The whole CRQ (in-cluding the dyspnoea domain) contains 20 questionsresponded to on a 7-point Likert-type scale, ranging from1 to 7 with lower scores indicating worse HRQoL. HRQoLwill additionally be measured by the EuroQol 5-

Dimension Questionnaire (EQ-5D-5 L) (EuroQoLGroup, www.euroqol.org) including a descriptive sys-tem for five dimensions (mobility, self-care, usualactivities, pain/ discomfort, anxiety/depression) as wellas a visual analogue scale for overall health state(feeling thermometer, see below) [29].

Physical activityPhysical activity will be assessed by the clinical visit ver-sion of PROactive Physical Activity in COPD Instrument(C-PPAC) in HOMEX-2 participants only. The C-PPACis a validated and reliable hybrid tool combining a shortpatient-reported outcome questionnaire and two activitymonitor variables (assessed by the ActiGraph® acceler-ometer, Pensacola, FL, USA) to measure physical activityin COPD patients in the two domains amount and diffi-culty (item scores 0–4, scale 0–100) [30, 31]. We willmeasure physical activity during one week prior to thebaseline and the 1-years follow-up visit.

Health status and symptomsHealth status and symptoms will be assessed by theCOPD Assessment Test (CAT) which measures the im-pact of COPD on a person’s health status (8 questions,6-point Likert-type scale) [32], the feeling thermometer(FT), a visual analogue scale for overall health state ran-ging from 0 (worst health you can imagine) to 100 (besthealth you can imagine) [33, 34], and of the HospitalAnxiety and Depression Scale (HADS) which assessessymptoms of depression and anxiety (14 questions,4-point Likert-type scale) [35].

Event based exacerbationsExacerbations are assessed patient-reported at 3-, 6- and12-months follow-up. Event-based definition requires anincrease in symptoms and an increase in dosage of ornew prescription of systemic corticosteroids and/orantibiotics.

Explanatory outcomesParticipants’ compliance and adherence to the exercisetraining programme (intervention group participantsonly) is assessed patient-reported as the percentage offulfilled training sessions according to the participants’handwritten reports in their exercise training books. Tominimise information bias, participants will be informedby their coaches to fill-in the training books regularlyand truthfully. Furthermore, compliance is assessed fromthe health care professionals’ perspective by evaluatingcoaches’ reports regarding exercise training interruptionof more than three consecutive days.Implementation feasibility and acceptability including

satisfaction and experience with the exercise trainingprogramme and health professionals’ feedback on the

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intervention will be assessed by a satisfaction question-naire and a brief semi-structured interview (participants)and/or focus groups (with participants and health profes-sionals separately) at 12-months follow-up. In addition, fi-delity to programme delivery will be assessed during theintervention period by the master coach.

Safety outcomesSerious adverse events (SAEs) that occur after baselineare sought by non-directive questioning of all partici-pants at 12-months follow-up. SAEs are also detectedwhen they are volunteered by the participants during thecourse of the study and, for intervention group

Table 1 Schedule of study visits and assessments

1) For T2 and T3 assessments, a questionnaire will be sent by mail to participants. At T3, study staff will also call the participants to verify in detail the questionsregarding cost-effectiveness and other exercise training2) Randomisation will be conducted at the end of visit T1, after all assessments have been conducted3) HOMEX-1 participants: measurements are already collected during rehabilitation; HOMEX-2 participants: a lung function measurement will be conducted by ahandheld spirometer4) HOMEX-2 only

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participants, at every contact. They are documented,their causal relationship with the intervention is assessedand they are reported to the responsible ethics commit-tee according to the legal requirements.

Assessments to adjust per-protocol analysisThe per-protocol analyses will be adjusted based on a newapproach proposed by Miguel Hernán [36] with the fol-lowing a priori specified factors: 1) Prognostic factors forthe primary outcome dyspnoea, 2) Adherence to conductthe exercises, and 3) Information whether the participantsconducted other strengthening exercise trainings (for de-tails see chapter Statistical analyses). Besides the prognos-tic factors which are already assessed by routinely plannedmeasurements, we will additionally assess self-efficacy toconduct the exercise training and information on otherexercise strength trainings by the participants.

Cost-effectiveness outcomesWe will conduct health economic analysis comparingthe relative costs and outcomes (effects) of the inter-vention and the comparator. Outcomes are assessedafter 3, 6 and 12-months and include 1) Direct health-care costs (patient-reported: physician visits, specialistvisits, number of hospitalisations, total number of hos-pitalisation days, number of days in rehabilitation /study-staff-reported: costs of working hours (adminis-tration of the intervention, trainings, supervision of the

intervention), costs of intervention material (elasticbands, training book); 2) Direct non-healthcare costs(patient-reported: ambulance transportations to hos-pital (travel costs to usual physician visits are not con-sidered), nursing home care); and 3) Indirect costs;mainly productivity loss costs (patient-reported: work-ing status and disability status due to COPD, workdayslost due to COPD and related adverse events).

Study visits and proceduresIn the course of the study, assessment visits areplanned at baseline (one visit for HOMEX-1 [T1] andtwo visits for HOMEX-2 [T0 and T1]) and at12-months follow-up (T4). The visits are conductedby trained study nurses at the same location; forHOMEX-1 at the PR clinics where the study partici-pants were recruited, for HOMEX-2 at the EBPI inZurich. In addition, after 3 (T2) and 6 (T3) months aquestionnaire including the CRQ, cost-effectivenessoutcomes, assessment of other exercise trainings andprognostic factors for dyspnoea will be sent by mailto all participants. At 6 months follow-up, study staffwill additionally call the participants to verify indepth responses regarding cost-effectiveness and otherexercise training. Figure 1 (1a: HOMEX-1, 1b:HOMEX-2) shows the study flow per participant andthe time schedule of study visits, assessments andintervention.

Fig. 1 Study flow per participant and overview on time schedule of study visits, assessments and intervention (1a: HOMEX-1, 1b: HOMEX-2)

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RandomisationParticipants will be randomised for each HOMEX-trialseparately, on the level of participants, with a 1:1 ratio,using block randomisation with varying block sizes, strati-fied by numbers of repetitions in the 1-min STS test (≤19vs. > 19 repetitions) and, for HOMEX-1 only, additionallystratified by study centre. Randomisation is performed bymeans of Research Electronic Data Capture (REDCap)[37], a secure, web-based application specifically designedto support data capture for research studies which ensuresconcealment of random allocation. A biostatistician fromthe EBPI who is not involved in the study created for bothHOMEX-trials a separate randomisation list using nQueryAdvisor® + nTerim® 4.0 (Statsols, Cork, Ireland). Anotherindependent researcher from the EBPI implemented theselists into the REDCap database. Randomisation will onlytake place after all baseline assessments are completed.

Blinding proceduresDue to the kind of intervention, neither participants norhealth care professionals can be blinded after the partici-pants’ assignment to the intervention or control group.Data analysts will be blinded to group assignment.

Withdrawal/discontinuation of participantsIf a participant withdraws consent, the primary reasonfor this decision will be recorded. The exercise trainingprogramme will be discontinued and no further assess-ments conducted. If a participant is unable to continuethe intervention for an extended period of time (assessedby the investigators regarding the specific participantand bearing in mind the participant’s personal situation),the participant is not considered withdrawn from thestudy. If he/she agrees, 12-months follow-up assess-ments will be conducted; if he/she refuses, follow-upassessments will be conducted at the time of discontinu-ation. Compliance/adherence to the study interventionwill be analysed by evaluation the training books, theconduct of the home visits and regular phone calls andthe records of the coaches’ reports.

Data managementData will be collected and managed using REDCap data-base hosted at the Clinical Trials Center (CTC) at theUniversity Hospital Zurich, Switzerland. Study nurses,coaches and designated investigator site staff will enterthe data; they will not be given access to the system untilthey have been trained. Automatic validation procedureswithin the system check for data discrepancies duringand after data entry and, by generating appropriate errormessages, allow the data to be confirmed or correctedonline by the designated investigator site staff.

Monitoring and quality assuranceAll study nurses are trained before study onset, a secondtraining will take place prior to the first 12-monthsfollow-up visit. EBPI study staff will conduct three moni-toring visits at each study centre; one 4 to 8 weeks afterthe conduction of the first baseline visit, a second aftercompletion of all baseline assessments and a thirdafter completion of all 12-months follow-up assessments.During these visits, the monitor will participate in onevisit and verify whether the participants’ instruction, dataassessment and randomisation are conducted accordingto protocol and check whether study procedures, docu-mentation and REDCap data entry are conducted cor-rectly. The monitor will check data entries of theprimary and secondary outcomes in the REDCap data-base. The monitoring records are discussed with thePrincipal Investigator and, if necessary, procedures arederived to improve the quality of data collection, pro-cesses, documentation and data entry.All coaches are fully trained before intervention on-

set. During the intervention a regular exchange be-tween coaches takes place by a protected forum. Inaddition, every 3 to 6 months meetings with all coachesare conducted for exchange purposes. The mastercoach accompanies all coaches during one of their firsthome visits, checks whether the elements of homevisits have been carried out according to the protocoland gives feedback to the coaches.

Sample sizeFor each of the two trials, the sample size calculation isbased on the primary outcome change in the CRQ dys-pnoea domain from baseline to 12-months follow-up. ForHOMEX-1, the hypothesis is maintenance in interventiongroup and decline in control group; for HOMEX-2, thehypothesis is improvement in the intervention group andmaintenance in control group. The well-established min-imal important difference of the CRQ dyspnoea scale is0.5 [38]. Assuming a standard deviation of the outcomevariable of 0.9 [2] (according to the literature we assumedthe same standard deviation of CRQ dyspnoea outcomesfor both patient populations, for those recently completingPR and for those who did not complete PR within the last2 years), 80% power and a significance level of 5% (two--sided), a sample size of 52 patients in each group is re-quired which results in a total sample size of 120 per trial,including a drop-out rate of 15% (patients for whomfollow-up assessments are not possible; sample size calcu-lator: http://hedwig.mgh.harvard.edu/sample_size/js/js_parallel_quant.html).

Statistical analysesAnalyses are conducted per trial separately. Baselinecharacteristics of the study participants are summarised

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according to numbers and percentages for qualitativevariables, mean and standard deviation for quantitativevariables with normal distribution and median and25th–75th percentiles for quantitative variables withnon-normal distribution. Differences in the change ofthe primary outcome CRQ dyspnoea from baseline to12-months follow-up between the intervention and con-trol group participants are compared by linear regressionanalyses corrected for stratification variables and, ifdeemed necessary due to baseline imbalances, potentialconfounders. The same analyses are used for continuoussecondary outcomes. Changes in CRQ dyspnoea overthe course of the year (assessed at 3, 6 and 12month)will be examined using linear mixed models. The ex-ploratory outcomes compliance to the training, satisfac-tion and health professionals’ feedback as well as theimplementation process parameters will be analysedwith a mixed-methods approach (using quantitative andthe appropriate qualitative methods). If there is a sub-stantial amount of missing values, we will compare theresults from the complete case analysis with the resultsfrom a multiple imputation approach.For the main analyses, we will use an intention-to-treat

approach, i.e., the study participants will be analysed ac-cording to the group which they were originally rando-mised to, regardless of whether they adhered to theintervention according to protocol. Missing follow-up dataof participants who did not conduct 12-months follow-upassessments will be substituted by the last available meas-urement (last observation carried forward).As a sensitivity analysis, we will additionally conduct a

per-protocol analysis, where we will keep only those par-ticipants in the intervention group who adhered to theintervention in terms of conducted exercise trainings[36]. We define adherence to protocol as “conduct ofexercise training sessions at least during 70% of theweeks within the year of intervention the participantswere able to train at least during 4 times a week”, i.e.,weeks when participants suffered from pulmonary exac-erbations or other serious health conditions that pre-vented them from training are not considered; asdiscussed with the coach (definition of a fulfilled indivi-dualised training session per day [according to protocol:3 different exercises per day are planned]: conduct of atleast 2 different exercises per day / definition of a ful-filled week of training [rate of training sessions accord-ing to protocol: 6 per week]: conduct of at least 3 out ofthe planned 6 individualised training sessions per weekon average).We will adjust the per-protocol analyses with prognos-

tic factors for the primary outcome dyspnoea (dyspnoea,lung function [FEV1], exercise capacity and events of ex-acerbations) and for adherence to conduct the exercises(self-efficacy to conduct the exercises, exercise capacity,

dyspnoea and acute worsening of health state [exacerba-tions and other]) and with the information whether thepatients conducted other exercise strength trainings.Concerning the control group, we will collect as muchinformation as possible, especially with respect to thetype and frequency of self-organised exercise training.This will also be included in the per-protocol analysis.The cost-effectiveness of the intervention and com-

parator will be assessed as cost per quality-adjusted lifeyear (QALY) gained. The analysis will be performedusing a time horizon of one year (i.e., equal to the max-imal follow-up of the trial) and using a societal perspec-tive. No interim analyses are planned.

DiscussionThe HOMEX-trials addresses two important and long-existing gaps in the context of PR. First, the study inter-vention provides an innovative way of making exercisetraining as accessible as possible for COPD patients byintroducing a minimal equipment and home-based exer-cise training programme together with a number of com-ponents that address important determinants at theindividual level, interpersonal level and environmentallevel for performing regular exercise training. Second, incontrast to many exercise training programmes that havebeen tested so far, the study intervention has a long-termperspective. It is important to highlight that the studyintervention aims to achieve long-term adherence to exer-cise training by providing a home-based programme thatis supported by health care professionals and others closeto the patients in order to address important determinantsfor performing exercise training.If our home-based minimal equipment exercise train-

ing programme proves to be effective long-term, it willfill the important gap of providing an easily accessibleand feasible option so that more COPD patients canfollow an exercise programme than it is currently thecase. Furthermore, it will also provide much neededevidence on how exercise training can be maintained inthe long-term. Thus, the HOMEX trials will addresstwo key scientific questions in the context of PR for pa-tients with COPD.In Switzerland, the Cantonal Lung Associations that

are covering the county already provide services both attheir centres and the patients’ homes. The proposedintervention has great potential to supplement existingservices with a long-term home-based exercise trainingprogramme option for COPD patients who either are notwilling or not able to participate in existing centre-basedprogrammes. The Swiss Lung Association could supportthe implementation by organizing and providing trainingand certification of health care professionals as well bysupporting communication and dissemination in their pa-tient population. Fortunately, the Swiss Lung Association

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has already expressed interest in taking over our home-based minimal equipment exercise training programmeand supports its implementation, because it fits well withtheir strategic goal of providing important patient-centredservices for individuals with COPD.

Abbreviations1-min STS: 1- Minute Sit-to-Stand Test; 6MWT: Six- Minute Walk Test;ATS: American Thoracic Society; CAT: COPD Assessment Test; COPD: ChronicObstructive Pulmonary Disease; CRQ: Chronic Respiratory Questionnaire;EBPI: Epidemiology, Biostatistics and Prevention Institute, University of Zurich;EQ-5D-5L: EuroQol 5-Dimension Questionnaire; FEV1: Forced expiratoryvolume in 1 s; FVC: Forced vital capacity; HADS: Hospital Anxiety andDepression Scale; HRQoL: Health-related Quality of Life; PR: PulmonaryRehabilitation; QALY: Quality adjusted life year; SD: Standard Deviation

AcknowledgementsWe warmly thank our advisory board Prof Anne Holland, La Trobe University,Melbourne, Australia, and Dr. Nick Hopkinson, Royal Brompton, London,Great Britain.

FundingHOMEX-1 is supported by the Research Fund of the Swiss Lung Association,Berne, and by the Research Fund of Klinik Barmelweid; HOMEX-2 is sup-ported by LUNGE ZÜRICH, Switzerland. The funding bodies had/have no rolein the design of the study, data collection, analysis and interpretation of dataand in writing the manuscript.

Availability of data and materialsNot applicable.

Authors’ contributionsAF, MAP, TR and KDL designed the conception and design of the two trials.JB contributed to the sections randomisation, sample size and statisticalanalyses. KDL and TR developed and piloted the HOMEX intervention, andRM contributed to the design of the HOMEX-2 trial. AF and RM drafted themanuscript. All authors read, revised and approved the final version of themanuscript.

Ethics approval and consent to participateBoth HOMEX trials were approved by the lead Ethics Committee KantonaleEthikkommission Zürich, and by the local ethics committees EthikkommissionBern and Ethikkommission Zentral- und Nordwestschweiz, Switzerland (BASEC-Nr. 2017–02092). All study participants will provide informed written consentbefore any study-related procedures are performed. The Ethics Committees willbe informed about important protocol modifications for approval.

Consent for publicationNot applicable.

Competing interestsThe authors declare that they have no competing or financial interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Received: 6 November 2018 Accepted: 15 February 2019

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