The Impact Of Covid-19 On A Large Pragmatic Clinical Trial Embedded In Primary Care

Abstract Introduction The COVID-19 pandemic has had significant impact on clinical care and traditional clinical trial operations, but it is unclear whether these impacts persist in pragmatic trials with a centralized study design. The Diuretic Comparison Project (DCP) is a Point-of Care pragmatic trial testing the hypothesis that chlorthalidone is superior to hydrochlorothiazide at the prevention of major cardiovascular (CV) events and non-cancer death. DCP relies on telephone consent, data collection from the electronic health record and Medicare, forgoes study visits, and limits provider time beyond usual care. DCP paused recruitment on VA directive in response to COVID-19 from 3/17/2020 until 7/1/2020. We assessed the impact of the COVID-19 pandemic on the centralized recruitment, patient follow-up, data collection, and outcome ascertainment performed in the DCP. Methods To assess clinical activity level and trial metrics, we compared data from two 8-month time periods: Pre-Pandemic (July 2019 – February 2020) and Mid-Pandemic (July 2020 – February 2021). Consent and randomization rates, study medication adherence, blood pressure (BP) and electrolyte follow-up rates, VA records of CV events, all-cause hospitalization, and death rates were compared for these two periods. Results Providers agreed to participate at a lower rate mid-pandemic (71%) than pre-pandemic (65%), but more patients were contacted (5,363 vs. 7,622) and consented (3,048 vs. 3,718) mid-pandemic. Patients refilled medications and remained on their randomized diuretic at the same frequency (90%) in both periods. Overall, rates of BP, electrolyte measurements, and hospitalizations decreased mid-pandemic while deaths increased. Conclusions While recruitment, enrollment, and adherence did not suffer during the pandemic, documented blood pressure checks and laboratory evaluations decreased, likely due to fewer in-person visits during the pandemic. All-cause VA hospitalizations decreased, despite a considerable number of COVID-related hospitalizations. While this suggests some changes in clinical care during the pandemic, the overall impact on DCP’s ability to operate mostly unimpacted during a global pandemic is another important strength of Point of Care clinical trials. Clinical Trial Registration NCT02185417 Registered 9 July 9 2014 https://clinicaltrials.gov/ct2/show/NCT02185417