CYCLE: A Randomized Clinical Trial of Early In-bed Cycling for Mechanically Ventilated Patients

Study Overview
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Brief Summary
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Patients who survive critical illness usually experience long-lasting physical and psychological impairments, which are often debilitating. Rehabilitation interventions started in the ICU may reduce this morbidity. In-bed cycling, which uses a special bicycle that attaches to the hospital bed, allows critically ill patients who are mechanically ventilated (MV) to gently exercise their legs while in the ICU. The main goal of this study is to determine whether critically ill MV adults recover faster if they receive early in-bed cycling than if they do not. Another objective is to determine whether in-bed cycling is a cost-effective intervention. 360 patients admitted to the ICU and receiving MV will be enrolled in the study. Following informed consent, patients will be randomized to either (1) early in-bed cycling and routine physiotherapy or (2) routine physiotherapy alone. Patients' strength and physical function will be measured throughout the study. If early in-bed cycling during critical illness improves short-term physical and functional outcomes, it could accelerate recovery and reduce long-term disability in ICU survivors.

Detailed Description
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Background: Survivors of critical illness have a long road of physical, cognitive, and psychological recovery. Although medical advances have reduced the mortality of critical illness, survival often comes with substantial long-term morbidity and societal cost. At 1-year follow-up,  35% of intensive care unit (ICU) survivors had sub-normal 6-minute walk distance, and  50% had not returned to work. Rehabilitation interventions started in the ICU may reduce this morbidity. In-bed cycling is a novel technology that may help critically ill, mechanically ventilated (MV) patients receive exercise very early to prevent or attenuate muscle weakness. Patients on MV typically receive prolonged bedrest and are often perceived as 'too sick' for physiotherapy (PT) interventions. However expert consensus and our previous multicentre pilot work suggest these interventions are safe. The CYCLE RCT will evaluate whether early in-bed cycling compared to usual PT interventions improves patient-reported outcomes. Objectives: CYCLE RCT: To determine if early in-bed cycling and routine PT compared to routine PT alone in critically ill, mechanically ventilated adults improves the primary outcome of physical function at 3 days after ICU discharge and secondary outcomes of strength, physical function, frailty, psychological distress, quality of life, mortality, and healthcare utilization. Economic Evaluation: To determine the cost-effectiveness of cycling and routine PT compared to routine PT alone among critically ill, mechanically ventilated adults. Design: 360-patient concealed open-label RCT with blinded outcome assessment Population: Critically ill adults receiving MV in a medical-surgical ICU Methods: After informed consent, patients will be randomized to receive 30 minutes/day of cycling, 5 days per week and routine PT interventions or routine PT interventions alone. Assessors, blinded to treatment allocation, will measure the primary outcome of patients' physical function at 3 days post-ICU. Secondary outcomes will be measured at ICU awakening, ICU discharge, 3 days post-ICU, hospital discharge, and 90-days post-enrollment. Relevance: By 2026, demand for ICU services is estimated to increase by 40% and more survivors will be at risk for post-ICU disability. If early cycling during critical illness improves short-term physical and functional outcomes, it could accelerate recovery and reduce long-term disability in ICU survivors.

Official Title
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CYCLE RCT: An International, Multi-centre, Randomized Clinical Trial of Early In-bed Cycling for Mechanically Ventilated Patients

Conditions
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Intensive Care Unit Acquired Weakness, Critical Care, Mechanical Ventilation, Respiratory Failure

Intervention / Treatment
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* Device: In-Bed Cycle Ergometer
* Other: Routine PT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is ≥ 18 years of age Patient is invasively mechanically ventilated ≤ 4 days Expected additional 2 day ICU stay Ability to ambulate independently (with or without gait aid) before their critical illness ICU length of stay ≤ 7 days Exclusion Criteria: Pre-hospital inability to follow simple commands in local language at baseline Acute conditions impairing ability to receive cycling Severe cognitive impairment pre-ICU Traumatic brain injury Acute proven or suspected central or peripheral neuromuscular weakness affecting the legs (e.g., stroke, Guillian-Barre syndrome, spinal injury) Temporary pacemaker (internal or external) Expected hospital mortality ≥ 90% Equipment unable to fit patient's body dimensions (elg., leg amputation, morbid obesity) Palliative goals of care Pregnancy (suspected or proven) Specific surgical exclusion as stipulated by surgery or ICU team Physician declines Cycling exemption not resolved during first 4 days of mechanical ventilation Patient already able to march on spot at time of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: In-Bed Cycle Ergometer + Routine PT<br>Patients will receive 30 minutes of in-bed cycling once per day, 5 days per week, while they remain in the ICU, for up to a maximum of 28 days. They will also receive routine physiotherapy. | Device: In-Bed Cycle Ergometer<br>* Physiotherapists will place the patient's legs in a specialized in-bed cycle ergometer allowing for gentle leg exercise. Exercise can performed in passive, active-assisted, or active mode.<br>* Other names: Restorative Therapies RT300 Supine;Other: Routine PT<br>* Includes, based on the patient's alertness and medical stability, activities to maintain or increase limb range of motion and strength, in- and out- of bed mobility, ambulation, and assistance with optimizing airway clearance and respiratory function.<br>|
| Active Comparator: Routine PT<br>Patients will receive routine physiotherapy interventions per current institutional practice | Other: Routine PT<br>* Includes, based on the patient's alertness and medical stability, activities to maintain or increase limb range of motion and strength, in- and out- of bed mobility, ambulation, and assistance with optimizing airway clearance and respiratory function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Function Test for ICU-scored (PFIT-s) | Patients complete 4 activities: arm and leg strength, ability to stand, and step cadence. Scores range from 0 to 10, with higher scores = better function. | 3 days after ICU discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Function Test for ICU-scored (PFIT-s) | Patients complete 4 activities: arm and leg strength, ability to stand, and step cadence. Scores range from 0 to 10, with higher scores = better function. | ICU Awakening, approximately 6 days after ICU admission; ICU Discharge, approximately 12 days after ICU admission; 3 days after ICU discharge; Hospital Discharge, approximately 28 days after ICU admission | 
| Muscle Strength | Manual muscle testing using the Medical Research Council (MRC) Scale. The patient exerts a force against the examiner's resistance. Each muscle is assessed on a 6-point scale (0 = no contraction, 5 = contraction sustained against maximal resistance). Scores range from 0 to 60, with higher scores = better strength. | ICU Awakening, approximately 6 days after ICU admission; ICU Discharge, approximately 12 days after ICU admission; 3 days after ICU discharge; Hospital Discharge, approximately 28 days after ICU admission | 
| 30 Second Sit to Stand | Patient completes as many sit to stand repetitions as possible in 30 seconds. Total number of repetitions is recorded as patient's score. Higher repetitions represent better function. | ICU Awakening, approximately 6 days after ICU admission; ICU Discharge, approximately 12 days after ICU admission; 3 days after ICU discharge; Hospital Discharge, approximately 28 days after ICU admission | 
| Two Minute Walk Test | Maximum distance walked in 2 minutes measured in metres on a continuous scale. | ICU Discharge, approximately 12 days after ICU admission; 3 days after ICU discharge; Hospital Discharge, approximately 28 days after ICU admission | 
| Patient-Reported Functional Scale-ICU (PRFS-ICU) | Assesses patient's perception of their physical function. Patients rate their ability to perform 6 mobility activities on a 0-10 scale (0=unable to perform activity, 10=able to perform activity at same level as before ICU admission). Scores range from 0 to 60, with higher scores representing better function. | ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission; 3 months after enrollment | 
| Katz Activities of Daily Living (ADL) Scale | Rates the patient's ability to complete 6 tasks: bathing, dressing, toileting, feeding, continence, and bed mobility. A rater assesses whether the patient is dependent or independent according to pre-specified criteria. Scores range from 0 to 6, with higher scores representing better function. | Baseline; ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission | 
| Clinical Frailty Scale | Patients are ranked on a scale from 1-9 according to level of frailty based on clinical descriptions (1 = very fit, 9 = terminally ill). | Baseline; hospital discharge, approximately 28 days after ICU admission | 
| Intensive Care Psychological Assessment Tool (IPAT) | Patients answer 10 questions related to critical care-related psychological distress. Scores range from 0-20, with scores of 7 or greater indicating a patient at risk of future psychological morbidity. | After ICU awakening assessment, approximately 7 days after ICU admission | 
| Health-Related Quality of Life - EuroQol-5D-5L | Five question self-administered, preference-based instrument to measure mobility, self-care, usual activities, pain, and anxiety/depression, as well as a visual analogue scale (VAS) global assessment of health. For each dimension, the participant chooses 1 of 5 levels that best describes their health on that day: no problem (1), slight (2), moderate (3), severe (4), or unable/extreme (5). The VAS is the participant's rating of their health on a scale of 0 worst health you can imagine to 100 best health you can imagine. | ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission; 3 months after enrollment | 
| Quality-Adjusted Life Years (QALYs) | A measure of health outcomes for economic evaluation that incorporates the impact of an intervention on both the quantity and quality of life. | 3 months after enrollment | 
| Mortality | Death in ICU, hospital, or post-discharge. | From study admission to 3 months after enrollment | 
| Hospital Discharge Location | For survivors: home, inpatient rehabilitation, other hospital, chronic care, assisted living facility, nursing home. | Hospital discharge, approximately 28 days after ICU admission | 
| Healthcare Utilization | Includes emergency room visits and hospitalizations, family doctor visits, specialist visits and outpatient clinics, other healthcare professional services. | From study admission to 3 months after enrollment | 
| Intervention and Healthcare Costs | Includes emergency room visits and hospitalizations, family doctor visits, specialist visits and outpatient clinics, assistive devices, renovations and modifications, other healthcare professional services, employment status and time off work, assistance from others. | From study admission to 3 months after enrollment | 
| Hospital Anxiety and Depression Scale (HADS) | Patient answers 14 questions related to anxiety and depression. Scores range from 0-21 with higher score indicating more distress. | 3 months after enrollment |