Implementation of a fully remote randomized clinical trial with cardiac monitoring
Authors: Mayfield Jacob J. , Chatterjee Neal A. , Noseworthy Peter A. , Poole Jeanne E. , Ackerman Michael J. , Stewart Jenell , Kissinger Patricia J. , Dwyer John , Hosek Sybil , Oyedele Temitope , Paasche-Orlow Michael K. , Paolino Kristopher , Friedman Paul A. , Waters Chloe , Moreno Jessica , Leingang Hannah , Heller Kate B. , Morrison Susan A. , Krows Meighan L. , Barnabas Ruanne V. , Baeten Jared , Johnston Christine ,   COVID-19 Early Treatment Team, Bole Medhavi , Braun Alyssa , Chu Helen Y. , Drummond Mark , Hauge Kirsten , Humphreys Madelaine , Hussein Abir , Johnston Christine , Kuntz Steve , Mathur Anya , McClellan Lindsey , Moreno Jessica , Pholsena Thepthara , Seymour Matthew , Stankiewicz-Karita Helen , Stewart Jenell , Taub Jina , Thuesmunn Zoe , Valinetz Ethan , Varon Dana , Wald Anna , Wood Brian , Dematteis Maianna , Wicklander Katie , Letterer Rebecca , Poole Jeanne , Sridhar Arun R. , Purcell Jeff , Kirk Mary , Waters Chloe D. , Baeten Jared M. , Barnabas Ruanne V. , Baugh Jennifer , Brown Clare E. , Celum Connie , Hamilton Daphne , Haugen Harald S. , Johnson Rachel , Knauer Jack , Liou Caroline H. , Morrison Susan , Quame-Amaglo Justice , Azaad  , Stalter Randy , Stewart Jenell , Thomas Katherine , Vazquez Vianey , Young Grant E. , Zia Yasaman , Zimmermann Azaad , Huang Meei-Li , Greninger Alexander L. , Jerome Keith R. , Wener Mark H. , Brown Deborah J. , Davenport Nathaniel , Gambito Omar , Arroyave Luisa , Bereznicka Agata , Berz Jonathan , Buitron Pablo , Camuso Michael , Cardoso Leticia , Cruz Ricardo , Dedier Julien , Dennaoui Husam , Goldman Anna , Henault Lori , Johnson Terrell , Koberna Sarah , Martinez Carlie , Martinez Erin , Ng Crystal , Paasche-Orlow Michael , Rogers Margot , Salerno Kathleen , Streed Carl , Truong Ve , Verma Nisha , Waite Katherine , Zalewski Steven , Brown Elizabeth R. , Dong Tracy Q. , Schiffer Joshua , Balthazar Chris , Bojan Kelly , Bouiri Hamid , Consignado Marisol , Davis Kortez , Dharmapuri Sadhana , Gonzalez Mireya , Hosek Sybil , Jackson Rachel , Malhotra Meenakshi , McFadden-Smith Antionette , McPherson Raymond , Muench Ryan , Oritz-Estes Ixchell , Oyedele Temitope , Rego Dorothy , Sanders Zoe Ellen , Seo-Lee Alisa , Simpson Karen , Ackerman Michael J. , Attia Zachi I. , Noseworthy Peter A. , Bendik Stefanie E. , Bershteyn Anna , Pitts Robert A. , Greco Peter , Klick Michelle , Paolino Kristopher M. , Anibaba Mueenah , Atkinson Evan , Campbell Mary Beth , Gomes Gerard , Hall Jacob , Huntwork John , Huntwork Margaret , Kissinger Patricia , Larkin Heather , Ntambwe Cedrick , Numbi Florice , Paloomares Michelle , Schmidt Norine , Rady Hamada , Ribando Maria , Triggs Daniel , Upadhyay Neha , Zheng Crystal , Sridhar Arun R. 
Published: December 2021

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.