Randomized Controlled Trial

. 2024 Oct 28:13:e54451.

doi: 10.2196/54451.

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

Diane Heels-Ansdell¹, Laurel Kelly², Heather K O'Grady³, Christopher Farley³, Julie C Reid^{1

3}, Sue Berney^{4

5}, Amy M Pastva⁶, Karen Ea Burns^{7

8}, Frédérick D'Aragon^{9

10

11}, Margaret S Herridge¹², Andrew Seely^{13

14}, Jill Rudkowski¹⁵, Bram Rochwerg^{1

15}, Alison Fox-Robichaud¹⁵, Ian Ball^{16

17}, Francois Lamontagne^{9

11}, Erick H Duan^{15

18}, Jennifer Tsang^{15

18}, Patrick M Archambault^{19

20

21}, Avelino C Verceles^{22

23}, John Muscedere²⁴, Sangeeta Mehta^{8

25}, Shane W English^{13

26

27}, Tim Karachi¹⁵, Karim Serri²⁸, Brenda Reeve²⁹, Lehana Thabane^{1

30}, Deborah Cook^{1

15

30}, Michelle E Kho^{2

3

30}

Affiliations

¹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
² Physiotherapy Department, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
³ School of Rehabilitation Science, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
⁴ Department of Physiotherapy, Austin Health, Heidelberg, Australia.
⁵ Department of Physiotherapy, The University of Melbourne, Parkville, Australia.
⁶ Duke University School of Medicine, Department of Orthopedic Surgery, Physical Therapy Division, Durham, NC, United States.
⁷ Li Sha King Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁸ Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
⁹ Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹⁰ Department of Anesthesiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹¹ Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹² Department of Medicine, Interdepartmental Division of Critical Care Medicine, Toronto General Research Institute, Institute of Medical Science, University Health Network, University of Toronto, Toronto, ON, Canada.
¹³ Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
¹⁴ Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹⁶ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
¹⁷ Department of Medicine, Western University, London, ON, Canada.
¹⁸ Division of Critical Care Medicine, Niagara Health, St. Catharines, ON, Canada.
¹⁹ Department of Anesthesiology and Intensive Care, Faculty of Medicine, Université Laval, Quebec, QC, Canada.
²⁰ Department of Family and Emergency Medicine, Université Laval, Québec, QC, Canada.
²¹ Centre de recherche intégrée pour un système apprenant en santé et services sociaux, Centre intégré de santé et de services sociaux de Chaudière-Appalaches, Lévis, QC, Canada.
²² Department of Medicine, University of Maryland Medical Centre, Midtown Campus, Baltimore, MD, United States.
²³ Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
²⁴ Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
²⁵ Department of Medicine, Sinai Health System, Toronto, ON, Canada.
²⁶ Department of Medicine (Critical Care), University of Ottawa, Ottawa, ON, Canada.
²⁷ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
²⁸ Critical Care Division, Department of Medicine, Centre de Recherche de Hôpital du Sacré-Cœur de Montréal, Hôpital Sacré-Coeur de Montréal, Montreal, QC, Canada.
²⁹ Department of Medicine, Brantford General Hospital, Brantford, ON, Canada.
³⁰ Research Institute of St. Joseph's, Hamilton, ON, Canada.

PMID: 39467285
PMCID: PMC11555464
DOI: 10.2196/54451

Randomized Controlled Trial

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

Diane Heels-Ansdell et al. JMIR Res Protoc. 2024.

. 2024 Oct 28:13:e54451.

doi: 10.2196/54451.

Authors

Affiliations

¹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
² Physiotherapy Department, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
³ School of Rehabilitation Science, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
⁴ Department of Physiotherapy, Austin Health, Heidelberg, Australia.
⁵ Department of Physiotherapy, The University of Melbourne, Parkville, Australia.
⁶ Duke University School of Medicine, Department of Orthopedic Surgery, Physical Therapy Division, Durham, NC, United States.
⁷ Li Sha King Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁸ Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
⁹ Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹⁰ Department of Anesthesiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹¹ Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹² Department of Medicine, Interdepartmental Division of Critical Care Medicine, Toronto General Research Institute, Institute of Medical Science, University Health Network, University of Toronto, Toronto, ON, Canada.
¹³ Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
¹⁴ Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹⁶ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
¹⁷ Department of Medicine, Western University, London, ON, Canada.
¹⁸ Division of Critical Care Medicine, Niagara Health, St. Catharines, ON, Canada.
¹⁹ Department of Anesthesiology and Intensive Care, Faculty of Medicine, Université Laval, Quebec, QC, Canada.
²⁰ Department of Family and Emergency Medicine, Université Laval, Québec, QC, Canada.
²¹ Centre de recherche intégrée pour un système apprenant en santé et services sociaux, Centre intégré de santé et de services sociaux de Chaudière-Appalaches, Lévis, QC, Canada.
²² Department of Medicine, University of Maryland Medical Centre, Midtown Campus, Baltimore, MD, United States.
²³ Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
²⁴ Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
²⁵ Department of Medicine, Sinai Health System, Toronto, ON, Canada.
²⁶ Department of Medicine (Critical Care), University of Ottawa, Ottawa, ON, Canada.
²⁷ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
²⁸ Critical Care Division, Department of Medicine, Centre de Recherche de Hôpital du Sacré-Cœur de Montréal, Hôpital Sacré-Coeur de Montréal, Montreal, QC, Canada.
²⁹ Department of Medicine, Brantford General Hospital, Brantford, ON, Canada.
³⁰ Research Institute of St. Joseph's, Hamilton, ON, Canada.

PMID: 39467285
PMCID: PMC11555464
DOI: 10.2196/54451

Abstract

Background: Survivors of critical illness are at risk of developing physical dysfunction following intensive care unit (ICU) discharge. ICU-based rehabilitation interventions, such as early in-bed cycle ergometry, may improve patients' short-term physical function.

Objective: Before unblinding and trial database lock, we describe a prespecified statistical analysis plan (SAP) for the CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) randomized controlled trial (RCT).

Methods: CYCLE is a 360-patient, international, multicenter, open-label, parallel-group RCT (1:1 ratio) with blinded primary outcome assessment at 3 days post-ICU discharge. The principal investigator and statisticians of CYCLE prepared this SAP with approval from the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes (including adverse events) and describes the planned primary, secondary, and subgroup analyses. The primary outcome of the CYCLE trial is the Physical Function Intensive Care Unit Test-scored (PFIT-s) at 3 days post-ICU discharge. The PFIT-s is a reliable and valid performance-based measure. We plan to use a frequentist statistical framework for all analyses. We will conduct a linear regression to evaluate the primary outcome, incorporating randomization as an independent variable and adjusting for age (≥65 years versus <65 years) and center. The regression results will be reported as mean differences in PFIT-s scores with corresponding 95% CIs and P values. We consider a 1-point difference in PFIT-s score to be clinically important. Additionally, we plan to conduct 3 subgroup analyses: age (≥65 years versus <65 years), frailty (Baseline Clinical Frailty Scale ≥5 versus <5), and sex (male versus female).

Results: CYCLE was funded in 2017, and enrollment was completed in May 2023. Data analyses are complete, and the first results were submitted for publication in 2024.

Conclusions: We developed and present an SAP for the CYCLE RCT and will adhere to it for all analyses. This study will add to the growing body of evidence evaluating the efficacy and safety of ICU-based rehabilitation interventions.

Trial registration: ClinicalTrials.gov NCT03471247; https://clinicaltrials.gov/ct2/show/NCT03471247 and NCT02377830; https://clinicaltrials.gov/ct2/show/NCT02377830.

International registered report identifier (irrid): RR1-10.2196/54451.

Keywords: critical illness; cycle ergometry; exercise therapy; mechanical ventilation; recovery of function; rehabilitation.

©Diane Heels-Ansdell, Laurel Kelly, Heather K O'Grady, Christopher Farley, Julie C Reid, Sue Berney, Amy M Pastva, Karen EA Burns, Frédérick D'Aragon, Margaret S Herridge, Andrew Seely, Jill Rudkowski, Bram Rochwerg, Alison Fox-Robichaud, Ian Ball, Francois Lamontagne, Erick H Duan, Jennifer Tsang, Patrick M Archambault, Avelino C Verceles, John Muscedere, Sangeeta Mehta, Shane W English, Tim Karachi, Karim Serri, Brenda Reeve, Lehana Thabane, Deborah Cook, Michelle E Kho. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.10.2024.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: Restorative Therapies (Baltimore, MD) provided 4 RT-300 supine cycle ergometers at Ottawa Civic Hospital, London Health Sciences (Victoria site), Duke University Medical Center, and the University of Maryland, Baltimore for this research. The funding sources and equipment manufacturer had no role in the design of this randomized trial and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.

Figures

**Figure 1**
CONSORT (Consolidated Standards of Reporting Trials) patient flow diagram.

See this image and copyright information in PMC

References

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous