HCQ trial halted over doubts on benefits
The preliminary results of the UK’s Recovery trial were released a day after a flawed study that raised safety concerns about hydroxychloroquine was retracted from the highly cited British medical journal, The Lancet, following scientific scrutiny.Updated: Jun 07, 2020 00:05 IST
A major trial of the anti-malarial drug hydroxychloroquine was halted in the UK on Friday after scientists found it provided “no benefit” for patients hospitalised with the coronavirus disease (Covid-19), but with several trials still under way, the last word is still awaited on the drug’s effectiveness against the viral ailment, scientists said.
The preliminary results of the UK’s Recovery trial were released a day after a flawed study that raised safety concerns about hydroxychloroquine was retracted from the highly cited British medical journal, The Lancet, following scientific scrutiny.
Following The Lancet study, the World Health Organization (WHO) suspended the hydroxychloroquine and chloroquine arm of its multi-country Solidarity Trail to validate four experimental Covid-19 treatments, but announced on Wednesday that the trials had been resumed. Researchers from the Recovery trial said they will share their data with the WHO.
The Recovery trial is a randomised clinical trial, considered the gold standard for clinical investigation, that used data from 11,000 patients in 175 hospitals in the UK to study the benefits of several experimental treatments against Covid-19. For the malaria drugs study, 1,542 patients were randomly assigned to hydroxychloroquine, and compared with 3,132 patients on standard hospital care.
Unlike previous trials that found increased risk of death, the Recovery trial found no significant difference in deaths between the two groups after 28 days. Treating patients with hydroxichloroquine did not shorten a patient’s hospital stay.
“If you are admitted to hospital, don’t take hydroxychloroquine. It doesn’t work,” said Martin Landray, professor of medicine and epidemiology at the University of Oxford, and deputy chief investigator of the Recovery trial, which has stopped recruiting patients on hydroxychloroquine treatment with immediate effect.
Another unrelated study from researchers in the US and Canada found hydroxychloroquine does not prevent disease when given within four days after high-risk or moderate-risk exposure to Covid-19. It was published in New England Journal of Medicine on June 3.
Some 203 Covid-19 trials with hydroxychloroquine are under way, 60 of which were focused on prophylaxis (preventive care), registered with ClinicalTrials.gov, the world’s the largest clinical trials database.
“We need to stop discussing hydroxychloroquine and wait for further study results. Unless there is clear evidence, it doesn’t help the public. Clinical trials must be completed, and that takes time,” Dr Soumya Swaminathan, chief scientist at WHO, told HT.
Hydroxychloroquine is a century-old malaria drug that is also approved for treating autoimmune conditions such as lupus and rheumatoid arthritis. It’s been in the spotlight as a possible treatment for Covid because of early studies in the laboratory that showed it reduces viral load, and for public endorsements from US President Donald Trump.
“Small in-vitro studies from China and Italy initially provided proof of concept by showing hydroxychloroquine lowered viral load. Its strong immunomodulatory properties are effective against autoimmune conditions like lupus and rheumatoid arthritis, which gave the legitimacy for its use against Covid-19, which may drive an unregulated immune response or cytokine storm. Since then, large studies like the Veterans’ trial in the US and the Recovery trial in the UK have found no benefits from hospitalised patients. The authors of the Veterans’ trial reanalysed their data after The Lancet debacle and stand by it,” said Dr N K Ganguly, former director general of the Indian Council of Medical Research.
As several trials on hydroxycholoroquine are still ongoing, the last word has not been said on the drug’s effectiveness, but there is need for a cautious approach, expert said.
“It’s a dynamic situation and should be reviewed periodically before a studied decision is taken at the national level. Till then, all treatment using hydroxychloroquine, whether as a prophylaxis or as treatment, must be done under strict clinical supervision and the highest quality of care,” said Dr Ganguly.
India is the world’s biggest producer of hydroxychloroquine, which is approved for use as a prophylaxis and has been given to asymptomatic health workers and contacts of Covid-19 patients since March 23. This was expanded to include frontline workers from May 22.
A study from India found that having four or more doses of hydroxychloroquine lowers the odds of getting infected with Sars-CoV-2, the virus that causes the coronavirus disease. The study, published in the Indian Journal of Respiratory Research earlier this week, said the malaria drug lowered the risk of infection by 80% if taken as recommended.
“Indiscriminate use, however, will make this drug redundant for malaria, which is endemic in India, so no one should have it without prescription,” said Dr Ganguly.
The Recovery trial will continue to study the evidence from other experimental treatments, which include a combination of antivirals drugs lopinavir and ritonavir used to treat HIV; low dose of the steroid dexamethasone used to reduce inflammation; the antibiotic azithromycin; and the anti-inflammatory drug tocilizumab, and convalescent plasma therapy that uses antibodies found in the blood of people who have recovered from Covid-19 to fight the virus.