Digital Silver Lining Seen in Failed COVID-19 Drug Trial

dr. Arun Sridhar shows the portable rhythm monitoring device used in the remote clinical trial. Credit: YOUR Medicine

Researchers show that study participants can be monitored safely and effectively at home for possible arrhythmic effects of drugs.

A clinical trial in which two test drugs failed to help patients with mild COVID-19 nevertheless had a silver lining: It proved the viability of a study model that safely and effectively monitors a drug’s potential arrhythmic side effects without the participants ever setting foot in it. a hospital or clinic.

The findings are reported today (Dec. 20, 2021) in the journal Communications Medicine. They also suggest that remote studies could extend clinical research to wider populations and significantly reduce the burden of time, travel and costs on participants, said Dr. Arun Sridhar, a senior author.

“This indicates that we can reach people who are typically unable to participate in research, including those who live far from academic health centers and those with limited mobility,” said Sridhar, an assistant professor of cardiology at the University of Washington. School of Medicine. “The digital age can help democratize clinical trials.”

The research was led by Drs. Arun Sridhar, left, and Christine Johnson, both of the University of Washington School of Medicine. Credit: YOUR Medicine

The fully remote survey was designed in early spring 2020 during the first wave of COVID-19. Researchers wanted to know whether the low-cost drugs hydroxychloroquine and azithromycin could speed up the recovery of patients who tested positive for the SARS-CoV-2 virus and treated themselves at home. However, the researchers 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 can cause cardiac arrest.

Daily electrocardiograms (ECG) would be required from participants, but concerns about COVID-19 prevented people from coming to the clinic for those tests.

As of April 15, 2020, COVID-19 patients in five U.S. healthcare systems began trial registration by phone or email, with consent confirmed by secure video conference call. Enrollees were provided with a 16-day kit of supplies to perform nasal swabs and obtain vital signs such as temperature and blood oxygen levels.

Also included: a handheld rhythm monitoring device to transmit digital EKGs to the research team in real time.

“At the beginning, all participants learned how to use the device and how to download the accompanying smartphone app. They were able to send an EKG to the study site during each day of the study to make sure the QT interval was not increasing,” said Dr. Christine Johnston, the study’s principal investigator and an associate professor of medicine at UW.

Approximately 218 patients were enrolled, started study medication, and sent ECG data to three randomized arms before the study was terminated for lack of drug benefit. Mayo Clinic staff processed the daily digital EKG readings. All measurements were typically forwarded to study coordinators and clinicians for review within one hour. Participants whose QT interval was high above baseline were immediately asked for another EKG, and if that test confirmed the finding, the medication was discontinued. Twenty-eight participants experienced prolonged QT, two of whom had to discontinue the drugs for that reason. No fatal events were reported.

More importantly, though, 85% of enrollees followed the study’s protocol of submitting one EKG per day for the first 14 days, suggesting remote self-monitoring for arrhythmias is possible, Johnston said.

“Before COVID, there was no precedent for remotely monitoring patients’ EKGs,” she said. “These participants were highly motivated and did well in terms of adherence to the daily examination of symptoms, Pap smears and EKG requests.”

Dozens of drugs, including some for arrhythmias and cancer, require patients to closely monitor their heart rhythms. In some cases, patients are hospitalized for the first three days to have two EKGs per day before the medication is considered safe enough to take at home.

“Remote monitoring can be a huge cost savings for the healthcare system and a huge time saver for patients, who don’t have to stay in the hospital for three days and miss work to get six EKGs,” said Sridhar. “Another advantage of remote trials is that we don’t need a dedicated clinical room that only serves subjects.”

The researchers noted two major limitations observed in the trial: a lack of digital literacy in older trial participants and the potential for poor communication with non-English speaking participants.

“Some elderly patients were not tech savvy with smartphones and apps. It was also slightly more difficult to communicate with non-English speaking patients in the study centers who did not have Spanish interpreters available. Sometimes younger relatives were asked to help bridge the communication gap,” Sridhar said.

“I think these barriers are relatively easy to overcome with stricter education for the participants, which we simply didn’t have time for with the pandemic.”

Reference: “Implementation of a fully remote randomized cardiac monitoring clinical trial” Dec 20, 2021, Communications Medicine.
DOI: 10.1038/s43856-021-00052-w

The research was funded by the Bill & Melinda Gates Foundation.