Implementation of a fully remote randomized clinical trial with cardiac monitoring
Jacob J. Mayfield, Neal A. Chatterjee, Peter A. Noseworthy, Jeanne E. Poole, Michael J. Ackerman, Jenell Stewart, Patricia Kissinger, John Dwyer, Sybil Hosek, Temitope Oyedele, Michael K. Paasche‐Orlow, Kristopher Paolino, Paul A. Friedman, Chloe Waters, Jessica Moreno, Hannah Leingang, Kate B. Heller, Susan Morrison, Meighan Krows, Ruanne V. Barnabas, Jared M. Baeten, Christine Johnston, COVID-19 Early Treatment Team, Medhavi Bole, Alyssa Braun, Helen Y. Chu, Mark W. Drummond, Kirsten Hauge, Madelaine Humphreys, Abir Hussein, Christine Johnston, Steve Kuntz, Anya Mathur, Lindsey McClellan, Jessica Moreno, Thepthara Pholsena, Matthew Seymour, Helen C. Stankiewicz Karita, Jenell Stewart, Jina M Taub, Zoe Thuesmunn, Ethan Valinetz, Dana Varon, Anna Wald, Brian Wood, Maianna Dematteis, Katie Wicklander, Rebecca Letterer, Jeanne E. Poole, Arun R. Sridhar, Jeff Purcell, Mary Ellen Kirk, Chloe Waters, Jared M. Baeten, Ruanne V. Barnabas, Jennifer Baugh, Clare Brown, Connie Celum, Daphne Hamilton, Harald S. Haugen, Rachel Johnson, Jack Knauer, Caroline H. Liou, Susan Morrison, Justice Quame‐Amaglo, Azaad, Randy M. Stalter, Jenell Stewart, Katherine K. Thomas, Vianey Vázquez, Grant E. Young, Yasaman Zia, Azaad Zimmermann, Meei‐Li Huang, Alexander L. Greninger, Keith R. Jerome, Mark H. Wener, Deborah J. Brown, Nathaniel Davenport, Omar Gambito, Luisa Arroyave, Agata Bereznicka, Jonathan P. B. Berz, P Buitrón, Michael Camuso, Leticia Cardoso, Ricardo Cruz, Julien Dedier, Husam Dennaoui, Anna L. Goldman, Lori Henault, Terrell K. Johnson, Sarah Koberna, Carlie Martinez, Erin Martinez, Crystal Ng, Michael K. Paasche‐Orlow, Margot Rogers, Kathleen Salerno, Carl G. Streed
Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has challenged researchers performing clinical trials to develop innovative approaches to mitigate infectious risk while maintaining rigorous safety monitoring. Methods: In this report we describe the implementation of a novel exclusively remote randomized clinical trial (ClinicalTrials.gov NCT04354428) of hydroxychloroquine and azithromycin for the treatment of the SARS-CoV-2-mediated COVID-19 disease which included cardiovascular safety monitoring. All study activities were conducted remotely. Self-collected vital signs (temperature, respiratory rate, heart rate, and oxygen saturation) and electrocardiographic (ECG) measurements were transmitted digitally to investigators while mid-nasal swabs for SARS-CoV-2 testing were shipped. ECG collection relied on a consumer device (KardiaMobile 6L, AliveCor Inc.) that recorded and transmitted six-lead ECGs via participants' internet-enabled devices to a central core laboratory, which measured and reported QTc intervals that were then used to monitor safety. Results: Two hundred and thirty-one participants uploaded 3245 ECGs. Mean daily adherence to the ECG protocol was 85.2% and was similar to the survey and mid-nasal swab elements of the study. Adherence rates did not differ by age or sex assigned at birth and were high across all reported race and ethnicities. QTc prolongation meeting criteria for an adverse event occurred in 28 (12.1%) participants, with 2 occurring in the placebo group, 19 in the hydroxychloroquine group, and 7 in the hydroxychloroquine + azithromycin group. Conclusions: Our report demonstrates that digital health technologies can be leveraged to conduct rigorous, safe, and entirely remote clinical trials.