HIV and ID Observations

Hydroxychloroquine — you knew that, right?

The headlines might read, Malaria Drug Ineffective in Preventing COVID-19 — but that doesn’t do justice to a remarkable clinical trial, just published this week in the New England Journal of Medicine.

Led by Dr. David Boulware at the University of Minnesota, the study asked this question:  Does hydroxychloroquine (HCQ) prevent the development of COVID-19 in people after significant healthcare or household exposure to the disease?

To say that the recruitment of this post-exposure prophylaxis trial was innovative hardly gives the methods enough credit. I first heard about the study in mid-March, based on this post by the lead author:

Healthcare worker exposed to COVID-19? Sharing a home with someone with COVID-19? Our Univ. of Minnesota team at the has launched a clinical trial studying a drug that may help prevent infection in those exposed to coronavirus. Email us at covid19@umn.edu to enroll.#IDTwitter pic.twitter.com/eFa425j2Z5

— David Boulware, MD MPH (@boulware_dr) March 17, 2020

It wasn’t long after reading this that I received a frantic message from one of my long-term patients with just this sort of high-risk exposure. I immediately referred him to the study.

With this study design, he didn’t have to fly to Minnesota to enroll — it was all done remotely. Informed consent, medication dispensing and shipment, adverse event monitoring, endpoint assessments.

(He did fine, by the way.)

In essence, this randomized, placebo-controlled study gives new meaning to the phrase “multicenter clinical trial”! I count 821 “centers” — specifically, the homes of the 821 participants, 414 of whom received HCQ, 407 placebo.

As the authors note, the conduct of the study had major advantages:

This approach allowed for recruitment across North America, minimized the risk of SARS-CoV-2 infection to researchers, lowered the burden of research participation, and provided a timely answer to this question of whether postexposure prophylaxis was effective. Moreover, this approach allowed broad geographic participation regardless of anyone’s physical distance from academic centers, increasing the generalizability of the findings.

Think also of the countless time, money, and effort saved by avoiding the need for local institutional review board approvals, clinical trials contracts, and study visits. Remarkable.

No, this isn’t the first study to enroll and follow participants remotely — the groundbreaking Physicians‘ and Nurses’ Health Studies come to mind. But it’s certainly the first one conducted and completed during a global pandemic.

For the record, the incidence of clinical COVID-19 illness did not differ significantly between groups (11.8% for HCQ, 14.3% placebo), and people receiving HCQ had more side effects, mostly gastrointestinal. There were no serious cardiac adverse events, a problem reported on other studies (especially when combined with azithromycin).

As noted in the accompanying editorial (and acknowledged by the authors), the study had several limitations, most notably the small proportion of COVID-19 cases (just over 10%) confirmed by PCR, and the delay (3 or more days) between exposure and starting preventive treatment. Furthermore, such a remotely conducted study cannot collect highly detailed data.

These and other limitations mean that these results may not be definitive; other prevention studies with HCQ continue.

Still, kudos to the investigators for so quickly carrying out this remarkable study. It’s a reminder that sometimes the innovation in clinical trials comes in the methods section, not in the results.