CYCLE Pilot Randomized Trial (CYCLE Pilot)

CYCLE Pilot: A Pilot Randomized Study of Early Cycle Ergometry Versus Routine Physiotherapy in Mechanically Ventilated Patients

St. Joseph's Healthcare Hamilton, Hamilton Health Sciences Corporation, Technology Evaluation in the Elderly Network / Canadian Frailty Network, Canadian Institutes of Health Research (CIHR), Ontario Lung Association, Canadian Respiratory Research Network

Background: Patients in the intensive care unit (ICU) are the sickest in hospital, and need advanced life-support. Survivors of critical illness are very weak and disabled. Up to 1 in 4 have severe leg weakness impairing their quality of life for as long as 5 years after ICU discharge. In-bed cycling involves use of special equipment that attaches to a patient's hospital bed, allowing them gentle exercise while in the ICU. Methods: Adult patients admitted to the ICU who need a breathing machine and are expected to survive their ICU stay are eligible. Patients will randomly receive 30 minutes of in-bed cycling each day they are in the ICU or routine physiotherapy, both delivered by specially trained physiotherapists. Outcomes: Feasibility: The investigators will study whether patients can cycle on most days of their ICU stay, whether patients and their families agree to be a part of the study, and whether investigators can systematically assess patients' strength. Relevance: Effective methods of physiotherapy are needed for critically ill patients to minimize muscle weakness, speed recovery, and improve quality of life. This pilot randomized study is the second of several future larger studies about in-bed cycling in the ICU. Our pilot work includes CYCLE Pilot and CYCLE Vanguard. CYCLE Pilot is an external pilot and enrolled 66 patients from 3/2015 to 6/2016. CYCLE Vanguard is an internal pilot and enrolled 47 patients from 11/2016 to 3/2018. CYCLE Vanguard patients will be analyzed in the main CYCLE RCT (NCT03471247).

Patients will receive 30 minutes of in-bed cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay

activities to assist with optimizing airway clearance and respiratory function, and, 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, and ambulation

Blinded outcome measures at hospital discharge (% outcomes at hospital discharge measured by blinded outcome assessors)

Physical Function Test for ICU (PFIT) at ICU awakening, ICU discharge, 3-days post-ICU discharge (CYCLE Vanguard only) and hospital 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

Muscle strength at ICU awakening, ICU discharge, 3-days post-ICU discharge (CYCLE Vanguard only), and hospital discharge

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 MRC scale (0=no contraction; 5=contraction sustained against maximal resistance).

Quadriceps strength at ICU and hospital discharge (Force measured in Kg and in Newtons on a continuous scale)

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.

5 question self-administered, preference-based instrument to measure mobility, self-care, usual activities, pain, and anxiety/ depression, as well as a global assessment of health

Inclusion Criteria: Adults admitted to a medical-surgical ICU within the 1st 4 days of mechanical ventilation (MV) and 1st 7 days of ICU, and could ambulate independently before hospital admission. Exclusion Criteria: Acute condition impairing patients' ability to cycle (e.g., leg fracture), proven or suspected neuromuscular weakness affecting the legs (e.g., stroke or Guillain-Barré syndrome), unable to follow commands in English pre-ICU, temporary pacemaker, expected hospital mortality >90%, unable to fit the bike, palliative goals of care, or persistent therapy exemptions in the 1st 4 days of MV (e.g., cardiorespiratory instability, active major bleeding)

Kho ME, Molloy AJ, Clarke FJ, Reid JC, Herridge MS, Karachi T, Rochwerg B, Fox-Robichaud AE, Seely AJ, Mathur S, Lo V, Burns KE, Ball IM, Pellizzari JR, Tarride JE, Rudkowski JC, Koo K, Heels-Ansdell D, Cook DJ. Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients. BMJ Open Respir Res. 2019 Feb 18;6(1):e000383. doi: 10.1136/bmjresp-2018-000383. eCollection 2019.

Takaoka A, Heels-Ansdell D, Cook DJ, Kho ME. The Association between Frailty and Short-Term Outcomes in an Intensive Care Unit Rehabilitation Trial: An Exploratory Analysis. J Frailty Aging. 2021;10(1):49-55. doi: 10.14283/jfa.2020.52.

Reid JC, McCaskell DS, Kho ME. Therapist perceptions of a rehabilitation research study in the intensive care unit: a trinational survey assessing barriers and facilitators to implementing the CYCLE pilot randomized clinical trial. Pilot Feasibility Stud. 2019 Nov 12;5:131. doi: 10.1186/s40814-019-0509-3. eCollection 2019.

McCaskell DS, Molloy AJ, Childerhose L, Costigan FA, Reid JC, McCaughan M, Clarke F, Cook DJ, Rudkowski JC, Farley C, Karachi T, Rochwerg B, Newman A, Fox-Robichaud A, Herridge MS, Lo V, Feltracco D, Burns KE, Porteous R, Seely AJE, Ball IM, Seczek A, Kho ME. Project management lessons learned from the multicentre CYCLE pilot randomized controlled trial. Trials. 2019 Aug 28;20(1):532. doi: 10.1186/s13063-019-3634-7. Erratum In: Trials. 2019 Oct 25;20(1):606.

Kho ME, Molloy AJ, Clarke F, Herridge MS, Koo KK, Rudkowski J, Seely AJ, Pellizzari JR, Tarride JE, Mourtzakis M, Karachi T, Cook DJ; Canadian Critical Care Trials Group. CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients. BMJ Open. 2016 Apr 8;6(4):e011659. doi: 10.1136/bmjopen-2016-011659.