Hydroxychloroquine is not effective when given late in mild-to-moderate COVID-19 patients, a new Brazilian study published in New England Journal of Medicine shows

Everyone wants to “follow the science.” However, with coronavirus claiming over half a million lives around the world, doctors and scientists are experimenting with promising drugs that could potentially save patients’ lives. One  of these drug is malaria drug hydroxycholoroquine.

On March 30, FDA issued emergency use authorization of hydroxychloroquine before it was later withdrawn on June 15 due to health and safety risks. FDA said, “in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of CQ and HCQ no longer outweigh the known and potential risks for the authorized use.”

We’ve been covering hydroxychloroquine for more than four months. On July 12, we wrote about another study from Henry Ford Health System that showed treatment with hydroxychloroquine cut the death rate significantly in sick patients hospitalized with COVID-19 – and without heart-related side-effects.

However, despite anecdotal evidence from doctors and physicians who credited hydroxycholoroquine for saving  patients’ lives, a new Brazilian study published in New England Journal of Medicine shows hydroxychloroquine is not effective when given late in mild-to-moderate COVID-19 patients.

According to NEJM, the research team conducted a three-group trial at 55 hospitals in Brazil. The trial included consecutive patients who were 18 years of age or older and who had been hospitalized with suspected or confirmed Covid-19 with 14 or fewer days since symptom onset.

However, the study did not provide detailed timeline of when the participants started the trial. Many front line doctors said hydroxychloroquine is effective only if the drug is taken early. For example, Dr. Harvey A. Risch, MD, PhD, a professor of epidemiology at Yale School of Public Health, said hydroxychloroquine has shown to be highly effective when the drug is given very early in the course of illness, especially when given in combination with the antibiotics azithromycin or doxycycline and the nutritional supplement zinc.

The trial was approved by the Brazilian National Commission for Research Ethics, the Brazilian Health Regulatory Agency (ANVISA), and ethics committees at the participating sites. The trial, which was funded by the hospitals and research institutes participating in Coalition Covid-19 Brazil,  found that among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, c clinical status at 15 days as compared with standard care.

Below is the abstract of the study.

BACKGROUND
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.

METHODS
We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.

RESULTS
A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.

CONCLUSIONS
Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123. opens in new tab.)