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

Respiratory Failure Clinical Trial

— CYCLE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03471247
• Other study ID #: CYCLE RCT
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 15, 2018
• Est. completion date: August 2024

Study information

• Verified date: May 2024
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: August 2024
• Est. primary completion date: May 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Care
• Intensive Care Unit Acquired Weakness
• Mechanical Ventilation
• Respiratory Failure
• Respiratory Insufficiency

Intervention

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:
• 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.

Locations

Country	Name	City	State
Australia	Austin Health - Austin Hospital	Heidelberg	Victoria
Canada	Brant Community Healthcare System - Brantford General Hospital	Brantford	Ontario
Canada	Hamilton Health Sciences - Hamilton General Hospital	Hamilton	Ontario
Canada	Hamilton Health Sciences - Juravinski Hospital	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Kingston Health Sciences Centre - Kingston General Hospital	Kingston	Ontario
Canada	Centre Integre de Sante et de Services Sociaux de Chaudiere-Appalaches - Hotel-Dieu de Levis	Lévis	Quebec
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	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	The Ottawa Hospital - Civic Campus	Ottawa	Ontario
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Centre Integre Universitaire de Sante et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System - St. Catharines Site	St. Catharines	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
United States	University of Maryland Medical Centre	Baltimore	Maryland
United States	Duke University Hospital	Durham	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
McMaster University	Canadian Critical Care Trials Group, Canadian Institutes of Health Research (CIHR), St. Joseph's Healthcare Hamilton

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (2)

Kho ME, Reid J, Molloy AJ, Herridge MS, Seely AJ, Rudkowski JC, Buckingham L, Heels-Ansdell D, Karachi T, Fox-Robichaud A, Ball IM, Burns KEA, Pellizzari JR, Farley C, Berney S, Pastva AM, Rochwerg B, D'Aragon F, Lamontagne F, Duan EH, Tsang JLY, Archambault P, English SW, Muscedere J, Serri K, Tarride JE, Mehta S, Verceles AC, Reeve B, O'Grady H, Kelly L, Strong G, Hurd AH, Thabane L, Cook DJ; CYCLE Investigators and the Canadian Critical Care Trials Group. 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. BMJ Open. 2023 Jun 23;13(6):e075685. doi: 10.1136/bmjopen-2023-075685. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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; Hospital Discharge, approximately 28 days after ICU admission
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of Mechanical Ventilation	Duration of invasive mechanical ventilation	From study admission to ICU discharge, approximately 10 days
Secondary	Length of stay	ICU and Hospital length of stay	From hospital admission to ICU discharge (approximately 14 days) and hospital discharge (approximately 21 days)
Secondary	Health-Related Quality of Life - EuroQol-5D-5L and Visual Analogue Scale	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
Secondary	Mortality	Death in ICU, hospital, or post-discharge.	From study admission to 3 months after enrollment
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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