Despite the myriad of evidence against the efficacy of hydroxychloroquine for the treatment of COVID-19, the number of people who still advocate for this remains stubbornly high. It’s a tale of belief trumping science, and it is one of the many fascinating things to emerge out of the global COVID pandemic.

Yet, a study released today should — once and for all — finally shut the coffin closed on hydroxychloroquine and COVID-19. The study — the Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) Study — was a randomized, double-blind, placebo-controlled clinical trial was conducted at 2 tertiary urban hospitals in Pennsylvania.

They enrolled full-time hospital-based healthcare workers (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists) between April 9, 2020 to July 14, 2020. They planned to enroll 200 subjects.

The trial randomized 132 healthcare workers to take 600 mg of hydroxychloroquine or placebo once a day for 8 weeks, and they tested whether this treatment will prevent infection with SARS CoV-2.

The study found absolutely no difference between the groups (6.3% for hydroxychloroquine vs 6.6% for placebo). In fact, because of futility, the trial was stopped early. This is why they only randomized 132 subjects rather than the planned 200.

This should be the end of hydroxychloroquine for COVID-19.

Now, it is understandable — given the novelty of the disease and the frightening nature of its effects on patients — that clinicians wanted to try anything and everything to treat COVID-19. If there was a treatment that may help, clinicians were using it. That’s how hydroxychloroquine started.

Yet, we need to make sure that any treatment we are administering, especially one with potential significant side effects like hydroxychloroquine, actually works. That’s where randomized trials come in. They are the best way to test whether a treatment actually works.

This study was a very good trial: it was randomized, which means that the subjects were randomly assigned to the two groups. It was double-blind, which means that the investigators and the subjects didn’t know if they received treatment or placebo. And it had a placebo group.

And it showed no effect of hydroxychloroquine.

Indeed, as the study authors rightly note, the study had some important limitations:

Our study was likely established with insufficient power. Given the small sample size, we cannot exclude the possibility of an undetected modest potential prophylactic effect of hydroxychloroquine.

We did not attempt to quantify the frequency of participant exposure or specific timing of exposures.

The cohort largely comprised young healthy HCWs and thus may not be generalizable to other populations with increased risk because of advanced age or additional comorbidities.

Both study hospitals were located in Philadelphia and may not be representative of COVID-19 prevalence and exposure risk in other geographical areas.

We cannot exclude the possibility that a lower or intermittent dose of hydroxychloroquine would be more effective at prevention, although a recent preclinical investigation in a COVID-19 macaque model did not find differences in antiviral activity with varied hydroxychloroquine dosing.

Despite these limitations, I think the study is quite an important contribution to the literature surrounding hydroxychloroquine and COVID-19. There are other ongoing prophylaxis trials, and I’m eagerly awaiting those results as well.

There are some who say that hydroxychloroquine helps zinc work its effect on SARS CoV-2. I looked this up on UpToDate, a clinical resource that I frequently use to keep me apprised on the latest literature, and there is no mention of hydroxychloroquine in combination with zinc. There are other trials around the world being conducted currently testing zinc in a number of combinations. That said, here is what the authors wrote about hydroxychloroquine:

According to a preliminary, unpublished report from a large randomized trial evaluating a number of potential therapies for hospitalized patients with COVID-19, there was no difference in 28-day mortality among 1561 patients who were randomly assigned to receive hydroxychloroquine compared with 3155 patients who received standard care (26.8 versus 25 percent, rate ratio 1.09, 95% CI 0.96–1.23); hydroxychloroquine also did not decrease length of hospital stay. Based on these data, the hydroxychloroquine arm of the trial was closed.

The World Health Organization also terminated the hydroxychloroquine arm of its large SOLIDARITY trial, and the United States National Institutes of Health terminated its trial of hydroxychloroquine in hospitalized patients; each cited a lack of benefit based on preliminary data from the trials.

So, to me, this prophylaxis trial — along with other big studies — should finally put to rest hydroxychloroquine for Covid-19. It simply doesn’t work.

And…if hydroxychloroquine really worked, President Trump would have gotten it. He has received monoclonal antibodies, remdesivir, and other therapies. Hydroxychloroquine was not on the list.

References:

1. RECOVERY trial investigators. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19
2. NIH halts clinical trial of hydroxychloroquine https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine
3. WHO. “Solidarity” clinical trial for COVID-19 treatments: Update on hydroxychloroquine. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments
4. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial.
   Tang W, Cao Z, Han M, et al. BMJ. 2020;369:m1849. Epub 2020 May 14.
5. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. Cavalcanti AB, Zampieri FG, Rosa RG, et al. N Engl J Med. 2020