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

• ClinicalTrials.gov Identifier: NCT03471247
• Recruitment Status: Active, not recruiting
• First Posted: March 20, 2018
• Last Update Posted: May 18, 2023
• Sponsor: McMaster University
• Collaborators: St. Joseph's Healthcare Hamilton; Canadian Institutes of Health Research (CIHR); Canadian Critical Care Trials Group
• Information provided by (Responsible Party): McMaster University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Intensive Care Unit Acquired Weakness; Critical Care; Mechanical Ventilation; Respiratory Failure	Device: In-Bed Cycle Ergometer; Other: Routine PT	Not Applicable

Detailed Description:

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:

1. 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.
2. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: CYCLE RCT: An International, Multi-centre, Randomized Clinical Trial of Early In-bed Cycling for Mechanically Ventilated Patients
• Actual Study Start Date: October 15, 2018
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: In-Bed Cycle Ergometer + Routine PT; 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; 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.; Other Name: Restorative Therapies RT300 Supine; Other: Routine PT; 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.
Active Comparator: Routine PT; Patients will receive routine physiotherapy interventions per current institutional practice	Other: Routine PT; 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.

Outcome Measures

Primary Outcome Measures :

1. Physical Function Test for ICU-scored (PFIT-s) [ Time Frame: 3 days after ICU discharge ]
   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.

Secondary Outcome Measures :

1. Physical Function Test for ICU-scored (PFIT-s) [ Time Frame: 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 ]
   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.
2. Muscle Strength [ Time Frame: 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 ]
   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.
3. 30 Second Sit to Stand [ Time Frame: 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 ]
   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.
4. Two Minute Walk Test [ Time Frame: ICU Discharge, approximately 12 days after ICU admission; 3 days after ICU discharge; Hospital Discharge, approximately 28 days after ICU admission ]
   Maximum distance walked in 2 minutes measured in metres on a continuous scale.
5. Patient-Reported Functional Scale-ICU (PRFS-ICU) [ Time Frame: ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission; 3 months after enrollment ]
   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.
6. Katz Activities of Daily Living (ADL) Scale [ Time Frame: Baseline; ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission ]
   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.
7. Clinical Frailty Scale [ Time Frame: Baseline; hospital discharge, approximately 28 days after ICU admission ]
   Patients are ranked on a scale from 1-9 according to level of frailty based on clinical descriptions (1 = very fit, 9 = terminally ill).
8. Intensive Care Psychological Assessment Tool (IPAT) [ Time Frame: After ICU awakening assessment, approximately 7 days after ICU admission ]
   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.
9. Health-Related Quality of Life - EuroQol-5D-5L [ Time Frame: ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission; 3 months after enrollment ]
   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".
10. Quality-Adjusted Life Years (QALYs) [ Time Frame: 3 months after enrollment ]
    A measure of health outcomes for economic evaluation that incorporates the impact of an intervention on both the quantity and quality of life.
11. Mortality [ Time Frame: From study admission to 3 months after enrollment ]
    Death in ICU, hospital, or post-discharge.
12. Hospital Discharge Location [ Time Frame: Hospital discharge, approximately 28 days after ICU admission ]
    For survivors: home, inpatient rehabilitation, other hospital, chronic care, assisted living facility, nursing home.
13. Healthcare Utilization [ Time Frame: From study admission to 3 months after enrollment ]
    Includes emergency room visits and hospitalizations, family doctor visits, specialist visits and outpatient clinics, other healthcare professional services.
14. Intervention and Healthcare Costs [ Time Frame: From study admission to 3 months after enrollment ]
    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.
15. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 3 months after enrollment ]
    Patient answers 14 questions related to anxiety and depression. Scores range from 0-21 with higher score indicating more distress.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Maryland

University of Maryland Medical Centre

Baltimore, Maryland, United States, 21201

United States, North Carolina

Duke University Hospital

Durham, North Carolina, United States, 27710

Australia, Victoria

Austin Health - Austin Hospital

Heidelberg, Victoria, Australia, 3084

Canada, Ontario

Brant Community Healthcare System - Brantford General Hospital

Brantford, Ontario, Canada, N3R 1G9

Hamilton Health Sciences - Hamilton General Hospital

Hamilton, Ontario, Canada, L8L 2X2

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada, L8N 4A6

Hamilton Health Sciences - Juravinski Hospital

Hamilton, Ontario, Canada, L8V 1C3

Kingston Health Sciences Centre - Kingston General Hospital

Kingston, Ontario, Canada, K7L 2V7

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada, N6A 5W9

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada, K1H 8L6

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, Canada, K1Y 4E9

Niagara Health System - St. Catharines Site

St. Catharines, Ontario, Canada, L2S 0A9

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Canada, Quebec

Centre Integre de Sante et de Services Sociaux de Chaudiere-Appalaches - Hotel-Dieu de Levis

Lévis, Quebec, Canada, G6V 3Z1

Centre Integre Universitaire de Sante et de Services Sociaux du Nord-de-L'Ile-de-Montreal - Hopital du Sacre-Coeur de Montreal

Montréal, Quebec, Canada, H4J 1C5

Centre Integre Universitaire de Sante et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada, J1H 5N4

Sponsors and Collaborators

McMaster University

St. Joseph's Healthcare Hamilton

Canadian Institutes of Health Research (CIHR)

Canadian Critical Care Trials Group

Investigators

• Principal Investigator: Michelle Kho, PT, PhD; McMaster University School of Rehabilitation Science

More Information

Publications:

Reid JC, Molloy A, Strong G, Kelly L, O'Grady H, Cook D, Archambault PM, Ball I, Berney S, Burns KEA, D'Aragon F, Duan E, English SW, Lamontagne F, Pastva AM, Rochwerg B, Seely AJE, Serri K, Tsang JLY, Verceles AC, Reeve B, Fox-Robichaud A, Muscedere J, Herridge M, Thabane L, Kho ME; CYCLE Investigators. Research interrupted: applying the CONSERVE 2021 Statement to a randomized trial of rehabilitation during critical illness affected by the COVID-19 pandemic. Trials. 2022 Sep 2;23(1):735. doi: 10.1186/s13063-022-06640-y.

• Responsible Party: McMaster University
• ClinicalTrials.gov Identifier: NCT03471247
• Other Study ID Numbers: CYCLE RCT
• First Posted: March 20, 2018
• Last Update Posted: May 18, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Respiratory Insufficiency; Respiration Disorders; Respiratory Tract Diseases