Rationale:
The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) guidance to report the impact of the pandemic on CYCLE and describe our mitigation approaches.
Methods
On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy), collect the primary outcome (physical function 3-days post-ICU discharge), and 90-day outcomes. We advised sites to prioritize data for the study’s primary outcome. We sought feedback on pandemic barriers related to trial procedures.
Results
As of March 17, 2020, 197 patients (of 360 planned) had been randomized; 26 (13.2%) remained in hospital or were pending 90-day assessments. From 15 active sites (12 Canada, 2 US, 1 Australia), we identified 5 patients still receiving the study intervention in ICUs, 6 requiring primary outcomes, and 17 requiring 90-day assessments. All ICU interventions (5/5, 100%), 5/6 (83%) of primary outcomes, and all (17/17, 100%) 90-day assessments were attempted. Out of the 6 primary outcomes, one site was unable to attempt due to a temporary institutional ban on direct patient contact for non-COVID research, 2 were attempted but not completed due to reasons unrelated to the pandemic, and 3 were completed. Our main mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, monitoring patient progress, data entry, and validation, and providing guidance for conducting some research activities remotely.
Conclusions
We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that there are other benefits to reporting mitigation strategies with the goal of improving research transparency and trial management.
Trial Registration:
NCT03471247