Background: The World Health Organization declared the outbreak of SARS-CoV-2 a pandemic on February 11, 2020. This organism causes COVID-19 disease and the rapid rise in cases and geographic spread strained healthcare systems. Clinical research trials were hindered by infection control measures discouraging physical contact and diversion of resources to meet emergent requirements. The need for effective treatment and prevention of COVID-19 prompted an untested investigational response. Trial groups adapted approaches using remote enrolment and consenting, newly developed diagnostic tests, delivery of study medications and devices to participants' homes, and remote monitoring to ensure investigator/enrollee safety while preserving ethical integrity, confidentiality, and data accuracy.
Methods: Clinical researchers at our community health system in the USA undertook an outpatient randomized open-label study of hydroxychloroquine (HCQ) prophylaxis versus observation of SARS-CoV-2 infection in household COVID-19 contacts. Designed in March 2020, challenges included COVID-19 infection in the research group, HCQ shortage, and lack of well-established home SARS-CoV-2 tests and remote ECG monitoring protocols in populations naive to these procedures. The study was written, funded, and received ethical committee approval in 4 months and was completed by September 2020 during a period of fluctuating infection rates and conflicting political opinions on HCQ use; results have been published. Singular methodology included the use of a new RNA PCR saliva SARS-CoV-2 home diagnostic test and a remote smartphone-based 6-lead ECG recording system.
Results: Of 483 households contacted regarding trial participation, 209 (43.3%) did not respond to telephone calls/e-mails and 90 (18.6%) declined; others were not eligible by inclusion or exclusion criteria. Ultimately, 54 individuals were enrolled and 42 completed the study. Numbers were too small to determine the efficacy of HCQ prophylaxis. No serious treatment-related adverse events were encountered.
Conclusions: Flexibility in design, a multidisciplinary research team, prompt cooperation among research, funding, ethics review groups, and finding innovative study approaches enabled this work. Concerns were balancing study recruitment against unduly influencing individuals anxious for protection from the pandemic and exclusion of groups based on lack of Internet access and technology. An issue to address going forward is establishing research cooperation across community health systems before emergencies develop.
Trial registration: ClinicalTrials.gov NCT04652648 . Registered on December 3, 2020.
Keywords: COVID-19 pandemic; Hydroxychloroquine; Prospective clinical trial; Remote ECG monitoring; SARS-CoV-2; Trial management.
© 2021. The Author(s).