Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients.

INTRODUCTION: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. METHODS AND ANALYSIS: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. ETHICS AND DISSEMINATION: Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Correction to: Project management lessons learned from the multicentre CYCLE pilot randomized controlled trial.

Following publication of the original article [1], we have been notified that one of the authors' names is spelled incorrectly. In this Correction the incorrect and correct author name are shown.

Project management lessons learned from the multicentre CYCLE pilot randomized controlled trial.

BACKGROUND: Clinical trials management can be studied using project management theory. The CYCLE pilot randomized controlled trial (RCT) was conducted to determine the feasibility of a future rehabilitation trial of early in-bed cycling in the intensive care unit (ICU). In-bed cycling is a novel intervention, not typically available in ICUs. Implementation of this intervention requires personnel with specialized clinical expertise caring for critically ill patients and use of the in-bed cycle. Our objective was to describe the implementation and conduct of our pilot RCT using a project management approach. METHODS: We retrospectively reviewed activities, timelines, and personnel involved in the trial. We organized activities into four project management phases: initiation, planning, execution, and monitoring and controlling. Data sources included Methods Centre documents used for trial coordination and conduct, and the trial data set. We report descriptive statistics as counts and proportions and also medians and quartiles, and we summarize the lessons learned. RESULTS: Seven ICUs in Canada participated in the trial. Time from research ethics board and contracts submission to first enrolment was a median (first quartile, third quartile) of 185 (146, 209) and 162 (114, 181) days, respectively. We trained 128 personnel on the CYCLE pilot RCT protocol, and 80 (63%) completed trial-related activities. Four sites required additional training after start-up due to staff turnover and leaves of absence. Over 15 months, we screened 864 patients: 256 were eligible and 66 were enrolled. Despite an 85% consent rate, 74% (190/256) of eligible patients were not randomized, largely (80% [152/190]) due to physiotherapist availability. Thirteen percent of recruitment weeks were lost due to physiotherapist staffing shortages. We highlight five key lessons learned: (1) prepare and anticipate site needs; (2) communicate regularly; (3) proactively analyse and act on process measure data; (4) develop contingency plans; (5) express appreciation to participating sites. CONCLUSIONS: Our analysis highlights the scope of relevant activities, rigorous training and monitoring, number and types of required personnel, and time required to conduct a multicentre ICU rehabilitation intervention trial. Our lessons learned can help others interested in implementing complex intervention trials, such as rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02377830 . Registered prospectively on 4 March 2015.

I SURVIVE: inter-rater reliability of three physical functional outcome measures in intensive care unit survivors.

PURPOSE: We prospectively assessed inter-rater reliability of three physical function measures in Canadian intensive care unit (ICU) survivors in the inpatient setting. METHODS: We enrolled patients who had an ICU length of stay of ≥ three days, were mechanically ventilated for ≥ 24 hr, and were ambulating independently before hospital admission. Weekly from ICU discharge to hospital discharge, two trained frontline clinicians, blinded to each other's findings, independently performed the Physical Function ICU Test-scored (PFIT-s; score out of 10), 30-sec sit-to-stand (30STS; # of stands), and two-minute walk test (2MWT; distance in m), all within 24 hr. We calculated the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal detectable change (MDC90). RESULTS: We enrolled 42 patients. PFIT-s: in 36 patients with 66 paired scores, the ICC was 0.78 (95% confidence interval [CI], 0.66 to 0.86), the SEM was 1.04, and the MDC90 was 2.42. 30STS: in 35 patients with 67 paired scores, the ICC was 0.85 (95% CI, 0.76 to 0.90), the SEM was 1.91, and the MDC90 was 4.45. 2MWT: in 35 patients with 58 paired scores, the ICC was 0.78 (95% CI, 0.66 to 0.87), the SEM was 20.87, and the MDC90 was 48.69. CONCLUSION: These three measures show good inter-rater reliability when used by trained frontline clinicians to assess physical function in ICU survivors in the inpatient setting.

RéSUMé: OBJECTIF: Nous avons évalué de manière prospective la fidélité interobservateurs de trois mesures de la capacité physique fonctionnelle auprès de survivants des unités de soins intensifs (USI) canadiennes dans un cadre hospitalier. MéTHODE: Nous avons recruté des patients qui avaient séjourné à l'USI ≥ trois jours, avaient été sous ventilation mécanique ≥ 24 h et se déplaçaient de façon autonome avant leur admission à l'hôpital. Entre le congé de l'USI et le congé de l'hôpital, deux cliniciens de première ligne formés ont réalisé chaque semaine et de manière indépendante trois tests : le PFIT (Test de la capacité physique fonctionnelle à l'USI - Physical Function ICU Test-scored; score sur 10), le test de 30 sec pour se lever d'une position assise (30STS; # de fois debout), et le test de marche pendant deux minutes (2MWT; distance en m). Les cliniciens n'avaient pas accès aux résultats de leur collègue. Nous avons calculé le coefficient de corrélation intraclasse (CCI), l'erreur type sur la mesure (ETM), et le changement minimal détectable (CMD90). RéSULTATS: Nous avons recruté 42 patients, et observé les résultats suivants : pour le PFIT : chez 36 patients avec 66 scores appariés, le CCI était de 0,78 (intervalle de confiance [IC] 95 %, 0,66 à 0,86), l'ETM de 1,04, et le CMD90 de 2,42; pour le test 30STS : chez 35 patients avec 67 scores appariés, le CCI était de 0,85 (IC 95 %, 0,76 à 0,90), l'ETM de 1,91, et le CMD90 de 4,45; pour le 2MWT : chez 35 patients avec 58 scores appariés, le CCI était de 0,78 (IC 95 %, 0,66 à 0,87, l'ETM de 20,87, et le CMD90 de 48,69. CONCLUSION: Ces trois mesures affichent une bonne fidélité interobservateurs lorsqu'elles sont utilisées par des cliniciens de première ligne formés afin d'évaluer la capacité physique fonctionnelle des survivants de l'USI dans un cadre hospitalier.

Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients.

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient's ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients. Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, patients underwent concealed randomisation to either 30 min/day of in-bed cycling and routine physiotherapy (Cycling) or routine physiotherapy alone (Routine) for 5 days/week, until ICU discharge. Our feasibility outcome targets included: accrual of 1-2 patients/month/site; >80% cycling protocol delivery; >80% outcomes measured and >80% blinded outcome measures at hospital discharge. We report ascertainment rates for our primary outcome for the main trial (Physical Function ICU Test-scored (PFIT-s) at hospital discharge). Results: Between 3/2015 and 6/2016, we randomised 66 patients (36 Cycling, 30 Routine). Our consent rate was 84.6 % (66/78). Patient accrual was (mean (SD)) 1.1 (0.3) patients/month/site. Cycling occurred in 79.3% (146/184) of eligible sessions, with a median (IQR) session duration of 30.5 (30.0, 30.7) min. We recorded 43 (97.7%) PFIT-s scores at hospital discharge and 37 (86.0%) of these assessments were blinded. Discussion: Our pilot RCT suggests that a future multicentre RCT of early in-bed cycling for MV patients in the ICU is feasible. Trial registration number: NCT02377830.

TryCYCLE: A Prospective Study of the Safety and Feasibility of Early In-Bed Cycling in Mechanically Ventilated Patients.

INTRODUCTION: The objective of this study was to assess the safety and feasibility of in-bed cycling started within the first 4 days of mechanical ventilation (MV) to inform a future randomized clinical trial. METHODS: We conducted a 33-patient prospective cohort study in a 21-bed adult academic medical-surgical intensive care unit (ICU) in Hamilton, ON, Canada. We included adult patients (≥ 18 years) receiving MV who walked independently pre-ICU. Our intervention was 30 minutes of in-bed supine cycling 6 days/week in the ICU. Our primary outcome was Safety (termination), measured as events prompting cycling termination; secondary Safety (disconnection or dislodgement) outcomes included catheter/tube dislodgements. Feasibility was measured as consent rate and fidelity to intervention. For our primary outcome, we calculated the binary proportion and 95% confidence interval (CI). RESULTS: From 10/2013-8/2014, we obtained consent from 34 of 37 patients approached (91.9%), 33 of whom received in-bed cycling. Of those who cycled, 16(48.4%) were female, the mean (SD) age was 65.8(12.2) years, and APACHE II score was 24.3(6.7); 29(87.9%) had medical admitting diagnoses. Cycling termination was infrequent (2.0%, 95% CI: 0.8%-4.9%) and no device dislodgements occurred. Cycling began a median [IQR] of 3 [2, 4] days after ICU admission; patients received 5 [3, 8] cycling sessions with a median duration of 30.7 [21.6, 30.8] minutes per session. During 205 total cycling sessions, patients were receiving invasive MV (150 [73.1%]), vasopressors (6 [2.9%]), sedative or analgesic infusions (77 [37.6%]) and dialysis (4 [2.0%]). CONCLUSIONS: Early cycling within the first 4 days of MV among hemodynamically stable patients is safe and feasible. Research to evaluate the effect of early cycling on patient function is warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01885442.

CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients.

INTRODUCTION: Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. METHODS AND ANALYSIS: 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0-4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1-2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. ETHICS AND DISSEMINATION: Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. TRIAL REGISTRATION NUMBER: NCT02377830; Pre-results.