Lancet Retracts Study Which Halted HCQ Trials For COVID-19 Treatment

Three of the authors of a study that halted the use of anti-malarial chloroquine or its analogue hydroxychloroquine for treatment of COVID-19 patients, retracted their paper on Thursday.

The Lancet said in a statement, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis”, have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they “can no longer vouch for the veracity of the primary data sources.” The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study, it said.

Today, three of the authors have retracted "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis" Read the Retraction notice and statement from The Lancet https://t.co/pPNCJ3nO8n pic.twitter.com/pB0FBj6EXr

— The Lancet (@TheLancet) June 4, 2020

The paper published on May 22 in the journal, suggested that treatment with the antimalarial drug chloroquine or its analogue hydroxychloroquine (taken with or without the antibiotics azithromycin or clarithromycin) offers no benefit for patients with COVID-19. The study analysed data from nearly 15,000 patients with COVID-19 receiving a combination of any of the four drug regimens and 81,000 controls.

Treatment with these medications among patients with COVID-19, either alone or in combination with macrolide antibiotics, was linked to an increased risk of serious heart rhythm complications in these patients.

Researchers suggest these treatment regimens should not be used to treat COVID-19 outside of clinical trials until results from randomised clinical trials are available to confirm the safety and efficacy of these medications for COVID-19 patients.

Chloroquine is an antimalarial drug and its analogue, hydroxychloroquine, is used to treat autoimmune diseases including lupus and arthritis. Both drugs have a good safety profile as treatments for those specific conditions, and the findings do not imply patients should stop taking these drugs if they are prescribed for approved conditions. They have also been shown to have antiviral effects in laboratory tests and are therefore of interest as potential treatments for COVID-19.

Prof Dr Mandeep R. Mehra, lead author of the study and Executive Director of the Brigham and Women’s Hospital Center for Advanced Heart Disease in Boston, USA, said: “This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death. Randomised clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for COVID-19 outside of clinical trials.” [1]

In the study, researchers analysed data from 96,032 patients hospitalised between 20 December 2019 and 14 April 2020 with laboratory confirmed SARS-CoV-2 infection from 671 hospitals. All of the patients included in the study had either been discharged or had died by 21 April 2020.

The team compared outcomes from patients treated with chloroquine alone (1,868), hydroxychloroquine alone (3,016), chloroquine in combination with a macrolide (3,783) or hydroxychloroquine with a macrolide (6,221). Patients from these four groups were compared with the remaining control group of 81,144 patients.

Some of the difference in the rates of mortality is due to underlying differences between patients who received the treatments and those who didn’t. After accounting for factors including age, race, body mass index and underlying health conditions including heart disease, lung disease and diabetes, the researchers found the drug regimens were associated with an increased risk of death.

Prof Dr. Frank Ruschitzka, Director of the Heart Center at University Hospital Zurich who also co-authored the study said: “Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19. Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus. However, previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed. However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”

Professor Christian Funck-Brentano, of the Sorbonne University in Paris, France (who was not involved in the study), said: “This well-conducted observational study adds to preliminary reports suggesting that chloroquine, hydroxychloroquine, alone or with azithromycin is not useful and may be harmful in hospitalized COVID-19 patients.”