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N. Avula, BA; Email: avula010@umn.edu

We thank the participants in the trial. We would also like to thank many others who made this trial possible, including The M Health Fairview Obesity Medicine Research Advisory Panel, particularly Stacy Dean and Yelena Kibasova. The numerous volunteers helped fold and tape boxes and place labels so that the study team could focus on enrollment and follow-up. Volunteers include Stacy Washington, Ben Tsech, Sasha Fraser, Evan Fraser, and Piotr Bednarski.

University of Minnesota, M Health Fairview: Program in Health Disparities Research; Clinical and Translational Science Institute’s (CTSI) Best Practices Integrated Informatics Core; Medical School Communications; M Health Fairview Recruiting Office; Department of Surgery Clinical Trials Office; Fairview Investigational Drug Services Pharmacy; Sponsored Projects Administration; Advanced Research and Diagnostic Laboratory; Center for Pediatric Obesity Medicine; UMN Institute for Engineering in Medicine; CTSI Regulatory support; Department of Medicine Research Operations and Division of General Internal Medicine, especially Jill Charles, and Kate Brekke.

Dr Bramante thanks her KL2 and K23 mentors for their continued career mentorship and support: Anne Joseph, MD, MPH; Aaron Kelly, PhD; Claudia Fox, MD, MPH; and Kimberly Gudzune, MD, MPH.

Dr Bramante thanks the M Health Fairview Learning Health Systems career development program and mentors Genevieve Melton-Meaux, MD, PhD and Bradley Benson, MD; and Fairview Research Services, especially Andrew Snyder and Jill Cordes. Dr Bramante also thanks other colleagues and mentors who contributed to considerations for the protocol: Eric Lenze, MD; Angela Reiersen, MD; David Haynes, PhD; Carlos Chaccour, MD; Ildilko Linvay, MD; Ana Palacio, MD; Leonardo Tamariz, MD, MPH; Ananth Shalev, MD; Erik Anderson, MD; and Jeanne M. Clark, MD, MPH.

JBB reports contracted fees and travel support for contracted activities for consulting work paid to the University of North Carolina by Novo Nordisk; grant support by Dexcom, NovaTarg, Novo Nordisk, Sanofi, Tolerion and vTv Therapeutics; personal compensation for consultation from Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Biomea Fusion Inc., Boehringer-Ingelheim, CeQur, Cirius Therapeutics Inc., Corcept Therapeutics, Eli Lilly, Fortress Biotech, GentiBio, Glycadia, Glyscend, Janssen, MannKind, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Sanofi, Stability Health, Terns Inc., Valo and Zealand Pharma; and stock/options in Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health. Dr Puskarich receives consulting fees from Opticyte and Cytovale.

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.

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Research Funding:

Dr Bramante was supported by grants (KL2TR002492 and UL1TR002494) from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) and by a grant (K23 DK124654) from the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH. Dr Buse was supported by a grant (UM1TR004406) from NCATS. Dr Nicklas was supported by a grant (K23HL133604) from the National Heart, Lung, and Blood Institute of the NIH. Dr Odde was supported by the Institute for Engineering in Medicine, UMN Office of Academic and Clinical Affairs COVID-19 Rapid Response Grant, the Earl E. Bakken Professorship for Engineering in Medicine, and by grants (U54 CA210190 and P01 CA254849) from the National Cancer Institute of the NIH. Dr Murray was supported in part by the Medtronic Faculty Fellowship. Dr Liebovitz receives funding from NIH RECOVER (OT2HL161847). Dr Siegel was supported by NIH grants (18X107CF6 and 18X107CF5) through a contract with Leidos Biomedical and by grants from National Heart, Lung, and Blood Institute of the NIH (T32HL129956), and the NIH (R01LM012982 and R21LM012744). Dr Puskarich receives grants from Bill and Melinda Gates Foundation (INV-017069), Minnesota Partnership for Biotechnology and Medical Genomics (00086722), National Heart, Lung, and Blood Institute of the NIH (OT2HL156812).

The trial was funded by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and the UnitedHealth Group Foundation.

Keywords:

  • Decentralized clinical trial
  • trial design
  • covid
  • remote research
  • randomized controlled trial

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

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Journal Title:

Journal of Clinical and Translational Science

Volume:

Volume 7, Number 1

Publisher:

, Pages e242-None

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2023

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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