Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2

Nandini Avula; Dustin Kakach; Christopher J Tignanelli; David M Liebovitz; Jacinda M Nicklas; Kenneth Cohen; Michael A Puskarich; Hrishikesh K Belani; John B Buse; Nichole R Klatt; Blake Anderson; Amy B Karger; Katrina M Hartman; Barkha Patel; Sarah L Fenno; Neha V Reddy; Spencer M Erickson; David R Boulware; Thomas A Murray; Carolyn T Bramante; COVID-OUT Trial Team

doi:10.1017/cts.2023.668

Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2

J Clin Transl Sci. 2023 Nov 7;7(1):e242. doi: 10.1017/cts.2023.668. eCollection 2023.

Authors

Nandini Avula¹, Dustin Kakach², Christopher J Tignanelli³, David M Liebovitz⁴, Jacinda M Nicklas⁵, Kenneth Cohen⁶, Michael A Puskarich^{7

8}, Hrishikesh K Belani⁹, John B Buse¹⁰, Nichole R Klatt³, Blake Anderson¹¹, Amy B Karger¹², Katrina M Hartman¹, Barkha Patel¹, Sarah L Fenno¹, Neha V Reddy¹, Spencer M Erickson¹, David R Boulware¹, Thomas A Murray¹³, Carolyn T Bramante¹; COVID-OUT Trial Team

Affiliations

¹ Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA.
² Investigational Drug Service, Fairview Health Services, University of Minnesota Medical Center, Minneapolis, MN, USA.
³ Department of Surgery, Medical School, University of Minnesota, Minneapolis, MN, USA.
⁴ Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁵ Department of Medicine, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.
⁶ UnitedHealth Group, Optum Health, Minnetonka, MN, USA.
⁷ Department of Emergency Medicine, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
⁹ Department of Medicine, Olive View - University of California, Los Angeles, CA, USA.
¹⁰ Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
¹¹ Atlanta Veterans Affairs Medical Center and the Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
¹² Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA.
¹³ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Abstract

The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT's are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.

Keywords: Decentralized clinical trial; covid; randomized controlled trial; remote research; trial design.