COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Horby P, Mafham M, Linsell L, et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2022926.
Abstract

BACKGROUND: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.

METHODS: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.

RESULTS: The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.

CONCLUSIONS: Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).

Ratings
Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Intensivist/Critical Care
Respirology/Pulmonology
Infectious Disease
Comments from MORE raters

Hospital Doctor/Hospitalists rater

Well constructed study that clarified an issue that has definite clinical implications for all those practicing during the pandemic. Anecdotally, this experience is very similar to what I personally experienced in caring for patients with COVID-19 in both a large urban hospital and a smaller suburban hospital. The concern about the potential for developing arrhythmias with this treatment was appropriate as I had a few patients who developed significant arrhythmias with hydroxychloroquine and azithromycin in combination. This study used a fairly heterogeneous sampling that represents closely what we are observing in real time, although the number of minorities in real time actually is higher than what we see represented in this study. Hopefully, this finally settles the question about this therapy and its lack of efficacy in this syndrome. The association with higher necessity for mechanical ventilation and mortality is concerning, although causality was not alleged.

Hospital Doctor/Hospitalists rater

A well performed randomized trial on hydroxychloroquine for COVID patients. Very useful information.

Infectious Disease rater

Upon a new evaluation and further beating, the dead horse remains dead.

Infectious Disease rater

This study has received a great deal of public press because it addresses a topic that became relevant to the general public because the coronavirus is such a novel and largely untreatable infection. The conclusion of the study was that hydroxychloroquine is very unlikely to help with important outcomes such as survival, early hospital discharge, and avoidance of mechanical ventilation. There were some numerically worse indicators in the hydoxychloroquine group, but the study (while large) was terminated because of futility of showing benefit and real concern about harm. It is difficult to imagine why there was such enthusiasm to set up a study of this kind without knowing that smaller and more poorly done studies offered a glimpse of potential benefit. While it is good to know that hydroxychloroquine has been well studied, I hope we can find better agents to treat this challenging disease.

Infectious Disease rater

This trial adds weight to the potential harm and no benefit of a refurbished drug that was widely promoted before definitive evidence would support it. It reminds us that caution should be exerted when considering medications based on preclinical studies and limited/preliminary data.

Intensivist/Critical Care rater

Well done and large study that should hopefully finally put the HCQ question to bed. Of note, SOLIDARITY pre-print just came out yesterday that showed the same thing (no benefit). The only thing to consider is that most have moved away from using HCQ in COVID as the data has been building for some time.

Internal Medicine rater

I think everyone who is aware of the media knows this by now.

Internal Medicine rater

One of the first reasonably sized RCTs on this topic.

Respirology/Pulmonology rater

This RCT finds that hydroxychloroquine did not reduce mortality in patients hospitalized with COVID-19. This research question has been fraught with controversy due to politicization, flawed preliminary studies and possible scientific misconduct. This large RCT is therefore very important for providing what should be the definitive answer: there is no benefit of HCQ in COVID-19.