Clinical trial NCT03471247: CYCLE: A Randomized Clinical Trial of Early In-bed Cycling for Mechanically Ventilated Patients
Official title: CYCLE RCT: An International, Multi-centre, Randomized Clinical Trial of Early In-bed Cycling for Mechanically Ventilated Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Intensive Care Unit Acquired Weakness
Critical Care
Mechanical Ventilation
Respiratory Failure
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: St. Joseph's Healthcare Hamilton
name: Canadian Institutes of Health Research (CIHR)
name: Canadian Critical Care Trials Group
First posted: 2018-03-20
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Physical Function Test for ICU-scored (PFIT-s)
timeFrame: 3 days after ICU discharge
Secondary outcomes:
measure: Physical Function Test for ICU-scored (PFIT-s)
timeFrame: ICU Awakening, approximately 6 days after ICU admission; ICU Discharge, approximately 12 days after ICU admission; Hospital Discharge, approximately 28 days after ICU admission
measure: Muscle Strength
timeFrame: 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
measure: 30 Second Sit to Stand
timeFrame: 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
measure: Two Minute Walk Test
timeFrame: ICU Discharge, approximately 12 days after ICU admission; 3 days after ICU discharge; Hospital Discharge, approximately 28 days after ICU admission
measure: Patient-Reported Functional Scale-ICU (PRFS-ICU)
timeFrame: ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission; 3 months after enrollment
measure: Katz Activities of Daily Living (ADL) Scale
timeFrame: Baseline; ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission
measure: Clinical Frailty Scale
timeFrame: Baseline; hospital discharge, approximately 28 days after ICU admission
measure: Intensive Care Psychological Assessment Tool (IPAT)
timeFrame: After ICU awakening assessment, approximately 7 days after ICU admission
measure: Duration of Mechanical Ventilation
timeFrame: From study admission to ICU discharge, approximately 10 days
measure: Length of stay
timeFrame: From hospital admission to ICU discharge (approximately 14 days) and hospital discharge (approximately 21 days)
measure: Health-Related Quality of Life - EuroQol-5D-5L and Visual Analogue Scale
timeFrame: ICU discharge, approximately 12 days after ICU admission; hospital discharge, approximately 28 days after ICU admission; 3 months after enrollment
measure: Mortality
timeFrame: From study admission to 3 months after enrollment
measure: Hospital Discharge Location
timeFrame: Hospital discharge, approximately 28 days after ICU admission
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 3 months after enrollment
measure: Quality-Adjusted Life Years (QALYs)
timeFrame: 3 months after enrollment
measure: Healthcare Utilization
timeFrame: From study admission to 3 months after enrollment
measure: Intervention and Healthcare Costs
timeFrame: From study admission to 3 months after enrollment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Medical Centre
state: Maryland
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Heidelberg
country: Australia
facility: Austin Health - Austin Hospital
state: Victoria
city: Brantford
country: Canada
facility: Brant Community Healthcare System - Brantford General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Hospital
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre - Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Civic Campus
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System - St. Catharines Site
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Lévis
country: Canada
facility: Centre Integre de Sante et de Services Sociaux de Chaudiere-Appalaches - Hotel-Dieu de Levis
state: Quebec
city: Montréal
country: Canada
facility: Centre Integre Universitaire de Sante et de Services Sociaux du Nord-de-L'Ile-de-Montreal - Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Integre Universitaire de Sante et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: McMaster University School of Rehabilitation Science
name: Michelle Kho, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.