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

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

Nandini Avula  1 , Dustin Kakach  2 , Christopher J Tignanelli  3 , David M Liebovitz  4 , Jacinda M Nicklas  5 , Kenneth Cohen  6 , Michael A Puskarich  7   8 , Hrishikesh K Belani  9 , John B Buse  10 , Nichole R Klatt  3 , Blake Anderson  11 , Amy B Karger  12 , Katrina M Hartman  1 , Barkha Patel  1 , Sarah L Fenno  1 , Neha V Reddy  1 , Spencer M Erickson  1 , David R Boulware  1 , Thomas A Murray  13 , Carolyn T Bramante  1 ; COVID-OUT Trial Team
Affiliations

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

Nandini Avula et al. J Clin Transl Sci. .

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.

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Conflict of interest statement

The fluvoxamine placebo tablets were donated by the Apotex pharmacy. The ivermectin placebo and active tablets were donated by the Edenbridge pharmacy. The funders had no influence on the design or conduct of the trial and were not involved in data collection or analysis, writing of the manuscript, or decision to submit for publication. The authors assume responsibility for trial fidelity and the accuracy and completeness of the data and analyses.

Figures

Figure 1.
Figure 1.
Decentralized operational elements of the COVID-OUT trial. Created with BioRender.com.
See this image and copyright information in PMC

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