Testing the feasibility of operationalizing a prospective, randomized trial with remote cardiac safety EKG monitoring during a pandemic

Abstract

Background: The coronavirus SARS-CoV-2 is highly contagious. Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2. The FDA authorized emergency use of HCQ against COVID-19. HCQ may have dose-related cardiotoxicity. This clinical trial received ethical approval on May 15, 2020, operationalized in June to evaluate a low prophylaxis dose of HCQ (200mg BID) in household contacts of COVID-19-positive patients without physical contact between investigators and participants. It represents the first report of the FDA approved 6-lead EKGs with a smartphone KardiaMobile® 6L application.

Methods: To reach a sample size of 170, household members were contacted by telephone, emailed consent forms with electronic signature capability, and randomized 2:1 to HCQ or observation for 10 days with follow-up of 14 days. Home saliva PCR tests recorded COVID status on days 1 and 14. Symptoms and 6-lead EKGs were obtained daily.

Results: Fifty-one participants were randomized with 42 evaluable at day 14. Remote monitoring of 407 EKGs revealed no QTc prolongation or other ECG changes in either group. At time of consent, no participants were symptomatic or COVID+. On days 1 and 14, COVID tests were positive in 4 and 2 in the HCQ group and 4 and 0 in the observation group. No tests converted to positive. There were no deaths or hospitalizations.

Conclusions: A clinical trial without personal contact, rapidly initiated and operationalized to exclude cardiac toxicity using daily remote 6-lead EKG monitoring, is feasible. Of 407 EKGs from 42 participants, there was no evidence of cardiac toxicity.

Clinical trial registration: Clinicaltrials.gov : NCT04652648 registration date: December 3, 2020.

Keywords: COVID-19; EKG monitoring; Hydroxychloroquine; Prospective trial; SARS-CoV-2.

Fig. 1

KardiaMobile® EKG display on smartphone with sensor below and sensor placed on leg with both thumbs in position

Fig. 2

Good quality ECG indicated by consistent isoelectric baseline and similar, well-defined T waves

Fig. 3

Poor quality ECG indicated by low voltage of T wave and significant variation of its terminal point between beats

Fig. 4

Poor quality ECG tracing indicated by significant motion artifact leading to poor isoelectric baseline. Additionally noted is an intraventricular conduction delay

Fig. 5

Enrollment, consent, and randomization process for study

Fig. 6

Daily EKG interval measurements in observation and HCQ groups

Fig. 7

COVID-19 saliva test results and symptoms in study participants