WHO Suspends Hydroxychloroquine Study Arm of COVID-19 Solidarity Trial

May 26, 2020

New data showed that treatment with hydroxychloroquine was associated with increased mortality in hospitalized patients with COVID-19. 

The World Health Organization (WHO) announced that it is temporarily pausing the hydroxychloroquine arm of its Solidarity Trial, which is evaluating the drug for use in coronavirus disease 2019 (COVID-19), as it reviews safety data.1

The suspension comes after data from the trial was published by The Lancet on Friday, May 22, which showed that treatment with hydroxychloroquine and chloroquine, with or without a macrolide, did not demonstrate in-hospital clinical benefits in patients with COVID-19. Moreover, the study authors reported an estimated higher mortality rate among patients receiving the drug, according to the findings.2

In a media briefing held on Monday, May 25, WHO Director-General Dr Tedros Adhanom Ghebreyesus announced that the Executive Group of the trial, representing 10 of the participating countries, has “agreed to review a comprehensive analysis and critical appraisal of all evidence available globally,” related to the use of the drug for COVID-19.1

“The review will consider data collected so far in the Solidarity Trial and in particular, robust randomized available data, to adequately evaluate the potential benefits and harms from this drug,” Dr Tedros Adhanom Ghebreyesus said in the briefing. The group has decided to implement a temporary pause of the hydroxychloroquine arm within the Solidary Trial while the safety data is reviewed by the Data Safety Monitoring Board. Other arms of the trial are continuing.1

The ongoing Solidarity Trial, which was initiated more than 2 months ago, aims to evaluate the safety and efficacy of 4 drugs and drug combinations against COVID-19. The recent data published in The Lancet resulted from an analysis of the use of hydroxychloroquine and chloroquine with or without macrolide for the treatment of COVID-19, using data from 671 hospitals in 6 continents. Approximately 96,000 hospitalized patients who tested positive for severe acute respiratory syndrome coronavirus 2 between December 20, 2019 and April 14, 2020 were included. Of these, 14,888 were in the treatment groups and 81,144 were in the control group.2

The 4 treatment groups were2:

  • Chloroquine alone

  • Chloroquine with a macrolide

  • Hydroxychloroquine alone

  • Hydroxychloroquine with a macrolide

The authors controlled for multiple confounding factors, such as age, sex, race or ethnicity, body mass index (BMI), underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity.2

When compared with mortality in the control group (9.3%), hydroxychloroquine (18.0%; hazard ratio 1.335, 95% CI 1.223-1.457), hydroxychloroquine with a macrolide (23.8%; 1.447, 1.386-1.531), chloroquine (16.4%; 1.365, 1.218-1.531), and chloroquine with a macrolide (22.2%; 1.368, 1.273-1.469) were each independently associated with an increased risk of in-hospital mortality.2

Additionally, compared with the control group (0.3%), hydroxychloroquine (6.1%; 2.369, 1.935-2.900), hydroxychloroquine with a macrolide (8.1%; 5.106, 4.106-5.983), chloroquine (4.3%; 3.561, 2.760-4.596), and chloroquine with a macrolide (6.5%; 4.011, 3.344-4.812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalization, according to the study.2

The authors noted that higher BMI appeared to be a risk marker for worse in-hospital survival in the study participants. The findings also suggested that drugs that stabilize cardiovascular function and improve endothelial cell dysfunction, such as ACE inhibitors, might improve prognosis.2

“These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomized clinical trials is needed,” they concluded.2

 

References:

1. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 25 May 2020. World Health Organization. May 25, 2020. Accessed May 26, 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---25-may-2020.

2. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet. 2020. DOI:https://doi.org/10.1016/S0140-6736(20)31180-6