A clinical trial in which two tested drugs failed to help patients with mild COVID-19 nonetheless had a silver lining: it proved the viability of a study design in which potential arrhythmic side effects medication are safely and effectively monitored without participants ever setting foot in a hospital or clinic.
The results are published on December 20, 2021 in the journal Communications Medicine. They also suggest that remote studies can extend clinical research to larger populations and dramatically reduce participant time, travel and costs, said lead author Dr Arun Sridhar.
This indicates that we can reach people who are generally unable to participate in research, including those who live far from academic health centers and those with reduced mobility. The digital age can help democratize clinical trials. “
Dr Arun Sridhar, Assistant Professor of Cardiology, Washington University School of Medicine
The fully remote study was designed in early spring 2020 during the first wave of COVID-19. Researchers wanted to know if the cheap drugs hydroxychloroquine and azithromycin could speed recovery for patients who tested positive for the SARS-CoV-2 virus and were self-healing at home. Investigators, however, were wary of the drugs’ potential to cause a type of heart rhythm disorder called a prolonged QT interval. If it persists, a long QT may cause cardiac arrest.
Daily electrocardiograms (ECGs) would be required for participants, but concerns over COVID-19 have kept people from coming to the clinic for these tests.
As of April 15, 2020, COVID-19 patients from five U.S. health systems began registering for the trial by phone or email, with consent confirmed by secure video conference. Registrants received a kit containing 16 days of supplies to perform nasal swab tests and obtain vital signs such as temperature and blood oxygen levels.
Also in the supply: a portable rhythm monitoring device to transmit digital ECGs to the research team in real time.
“In the beginning, all participants learned how to use the device and download the corresponding smartphone app. They could transmit an ECG to the study site during each day of the study to ensure that the QT interval was not increasing, ”said Dr. Christine Johnston, principal investigator of the trial and associate professor of medicine at UW.
Some 218 patients were enrolled, started on study drug, and passed ECG data to three randomized arms before the end of the trial for lack of drug benefit. Mayo Clinic collaborators processed the daily digital ECG readings. All readings were forwarded to trial coordinators and clinicians for review, usually within an hour. Participants whose QT interval was elevated above baseline were promptly instructed to take another ECG, and if this test confirmed the result, the drug was discontinued. Twenty-eight participants experienced prolongation of the QT interval, two of whom had to discontinue medication for this reason. No fatal events have been reported.
More importantly, 85% of those enrolled followed the trial protocol to submit one ECG daily for the first 14 days, suggesting that remote arrhythmia self-monitoring is possible, Johnston said.
“Before COVID, there was no precedent for monitoring patient ECGs remotely,” she said. “These participants were highly motivated and did well in terms of adhering to the daily symptom survey, swabs, and ECG requests.”
Dozens of drugs, including some for arrhythmias and cancer, require patients to have their heart rhythms closely monitored. In some cases, patients are admitted to the hospital for the first three days to have two ECGs per day before the drug is deemed safe enough to be taken at home.
“Remote monitoring could generate huge savings for healthcare systems and a huge time saver for patients, who wouldn’t have to stay in the hospital for three days and take time off work just to get six ECGs, ”Sridhar said. “Another advantage of remote trials is that it doesn’t require us to have a dedicated clinical space that only serves test subjects.”
The researchers noted two main limitations seen with the trial: a lack of digital literacy among older trial participants and the potential for poor communication with non-English speaking participants.
“Some older patients weren’t tech-savvy with smartphones and apps. It was also slightly more difficult to communicate with non-English speaking patients in the trial centers that didn’t have Spanish interpreters. was asking younger family members to help bridge the communication gap, ”Sridhar said.
“I think these obstacles are relatively easy to overcome with more rigorous education for the participants, which is why we just didn’t have time with the pandemic.”
The study was funded by the Bill & Melinda Gates Foundation.
Washington University School of Medicine / UW Medicine
Mayfield, JJ, et al. (2021) Implementation of a fully remote randomized clinical trial with cardiac monitoring. Communications medicine. doi.org/10.1038/s43856-021-00052-w.