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

NCT ID: NCT03471247

Last Updated: 2024-05-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-15
• Study Completion Date: 2024-08-31

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.

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.

Conditions

Intensive Care Unit Acquired Weakness; Critical Care; Mechanical Ventilation; Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

In-Bed Cycle Ergometer

Intervention Type: DEVICE

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.

Routine PT

Intervention Type: OTHER

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.

Routine PT

Patients will receive routine physiotherapy interventions per current institutional practice

Group Type: ACTIVE_COMPARATOR

Routine PT

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DEVICE

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.

Intervention Type: OTHER

Other Intervention Names

Restorative Therapies RT300 Supine

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Joseph's Healthcare Hamilton

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Canadian Critical Care Trials Group

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle Kho, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University School of Rehabilitation Science

Locations

University of Maryland Medical Centre

Baltimore, Maryland, United States

Duke University Hospital

Durham, North Carolina, United States

Austin Health - Austin Hospital

Heidelberg, Victoria, Australia

Brant Community Healthcare System - Brantford General Hospital

Brantford, Ontario, Canada

Hamilton Health Sciences - Hamilton General Hospital

Hamilton, Ontario, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Hamilton Health Sciences - Juravinski Hospital

Hamilton, Ontario, Canada

Kingston Health Sciences Centre - Kingston General Hospital

Kingston, Ontario, Canada

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, Canada

Niagara Health System - St. Catharines Site

St. Catharines, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

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

Lévis, Quebec, Canada

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

Montreal, Quebec, Canada

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

Sherbrooke, Quebec, Canada

Countries

United States; Australia; Canada

References

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.

Reference Type: BACKGROUND

PMID: 36056378 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37355270 (View on PubMed)

Heels-Ansdell D, Kelly L, O'Grady HK, Farley C, Reid JC, Berney S, Pastva AM, Burns KE, D'Aragon F, Herridge MS, Seely A, Rudkowski J, Rochwerg B, Fox-Robichaud A, Ball I, Lamontagne F, Duan EH, Tsang J, Archambault PM, Verceles AC, Muscedere J, Mehta S, English SW, Karachi T, Serri K, Reeve B, Thabane L, Cook D, Kho ME. Early In-Bed Cycle Ergometry With Critically Ill, Mechanically Ventilated Patients: Statistical Analysis Plan for CYCLE (Critical Care Cycling to Improve Lower Extremity Strength), an International, Multicenter, Randomized Clinical Trial. JMIR Res Protoc. 2024 Oct 28;13:e54451. doi: 10.2196/54451.

Reference Type: DERIVED

PMID: 39467285 (View on PubMed)

Kho ME, Berney S, Pastva AM, Kelly L, Reid JC, Burns KEA, Seely AJ, D'Aragon F, Rochwerg B, Ball I, Fox-Robichaud AE, Karachi T, Lamontagne F, Archambault PM, Tsang JL, Duan EH, Muscedere J, Verceles AC, Serri K, English SW, Reeve BK, Mehta S, Rudkowski JC, Heels-Ansdell D, O'Grady HK, Strong G, Obrovac K, Ajami D, Camposilvan L, Tarride JE, Thabane L, Herridge MS, Cook DJ. Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients. NEJM Evid. 2024 Jul;3(7):EVIDoa2400137. doi: 10.1056/EVIDoa2400137. Epub 2024 Jun 12.

Reference Type: DERIVED

PMID: 38865147 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CYCLE RCT

Identifier Type: -

Identifier Source: org_study_id