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
{"title":"对机械通气的重症患者进行早期床上自行车负重训练:国际多中心随机临床试验 CYCLE(危重症患者骑自行车提高下肢力量)的统计分析计划。","authors":"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","doi":"10.2196/54451","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03471247; https://clinicaltrials.gov/ct2/show/NCT03471247 and NCT02377830; https://clinicaltrials.gov/ct2/show/NCT02377830.</p><p><strong>International registered report identifier (irrid): </strong>RR1-10.2196/54451.</p>","PeriodicalId":14755,"journal":{"name":"JMIR Research Protocols","volume":"13 ","pages":"e54451"},"PeriodicalIF":1.4000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555464/pdf/","citationCount":"0","resultStr":"{\"title\":\"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\":\"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\",\"doi\":\"10.2196/54451\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03471247; https://clinicaltrials.gov/ct2/show/NCT03471247 and NCT02377830; https://clinicaltrials.gov/ct2/show/NCT02377830.</p><p><strong>International registered report identifier (irrid): </strong>RR1-10.2196/54451.</p>\",\"PeriodicalId\":14755,\"journal\":{\"name\":\"JMIR Research Protocols\",\"volume\":\"13 \",\"pages\":\"e54451\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555464/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JMIR Research Protocols\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2196/54451\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEALTH CARE SCIENCES & SERVICES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JMIR Research Protocols","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2196/54451","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEALTH CARE SCIENCES & SERVICES","Score":null,"Total":0}
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.
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.