Coronavirus | No WHO bar on India testing HCQ as a preventive drug, says WHO chief scientist Soumya Swaminathan

However, India should do stricter trials on hydroxychloroquine efficacy, Dr. Swaminathan says.

A pharmacist displays a box of hydroxychloroquine (HCQ) tablets in his store in Hyderabad. File

The World Health Organisation’s (WHO) moratorium on testing hydroxychloroquine (HCQ), the controversial anti-malarial drug, for treating COVID-19 , which was announced on Monday, doesn’t imply that India should pause testing the drug as a preventive, Dr. Soumya Swaminathan, Chief Scientist, WHO, told The Hindu in an email. However, she stressed that India ought to be doing stricter trials to test the drug’s efficacy in staving off infection in asymptomatic people at high-risk of contracting the virus.

HCQ was one of four drug-combinations being tested in a global clinical trial, called Solidarity Trial, coordinated by the WHO.

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Four hundred hospitals in 35 countries would be comparing the benefits to COVID patients from taking either Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and hydroxychloroquine. They are all drugs for other diseases but have shown varying degrees of promise in blunting COVID-19 infection.

To objectively assess the benefit of these drugs over standard-of-care treatments, clinicians would be assessing these drugs in Randomised Clinical Trial (RCT) — the most medically legitimate approach — whereby some groups of patients, unknown to the administering doctors and recipient patients — would get the drug and some wouldn’t.

While these studies are in progress and still actively recruiting patients, a spate of studies have shown that HCQ shows no benefit — in fact, it puts patients at greater harm.

The latest such study published in the medical journal Lancet found that in 96,000 hospitalised SARS-CoV-2 patients across six continents, there was no benefit — even additional harm of cardiac arrhythmia — in those being treated with HCQ.

However, this study wasn’t a clinical trial and was an observational study in which all participants get the treatment.

However, officials in the Health Ministry said India’s stance — recommending the drug as a preventive for groups that were at high risk of contracting the infection — was based on internal studies and laboratory experiments that showed the drug had anti-viral properties. “India has so far made the right decision on HCQ and that this decision has been based on evidence,” Preeti Sudan, Secretary, Ministry of Health and Family Welfare, told The Hindu .

“WHO is not advising stopping all HCQ trials... the suspension of enrolment applies only to the Solidarity trial. Many prophylaxis trials using HCQ are ongoing or about to start,” Dr. Swaminathan said.

On May 4, the Indian Council of Medical Research (ICMR) formally published plans for a clinical trial — again an observational trial — that will check if 2,000 doctors, healthcare and sanitation workers who work in five dedicated COVID-19 hospitals across the country were afforded any protection while taking a prescribed course of HCQ.

Dr. Swaminathan said HCQ, even for testing its potency as a prophylactic, ought to be tested via the RCT method.

“WHO has consistently said that the best way of proving the efficacy of a drug for prevention or treatment is through well conducted randomised clinical trials. Observational studies are always subject to the risk of bias and can sometimes produce misleading results. In the case of HCQ, there is no clear evidence from RCTs on either safety or efficacy, so that would be the best way to proceed,” she said.

It was “very rare”, for a drug to fail at treating moderate or severe disease but to be effective in working as a preventive, added Dr. Swaminathan, who was formerly Director-General of the ICMR.

Director-General of ICMR Balram Bhargava said at a press conference on Tuesday that while several studies were ongoing in India, there “was evidence” that the drug worked as prophylactic. “It is difficult to do a randomised trial for a drug that may be working. We’ve got some observational data. A more detailed study will be available soon. We’ve weighed the risks and benefits and concluded that we can’t as of now deny this to our frontline workers battling COVID-19.”

The government late last week extended the use of HCQ for paramilitary and police personnel involved in COVID-19 management, besides direct health care providers for positive patients. It cited three separate studies that claimed benefits but hasn’t publicised details of these studies.

HCQ, said Dr. Bhargava, had a history of safe use. Widely prescribed as prophylaxis and treatment for malaria as well as rheumatoid arthritis and lupus (both disorders of the immune system) in India, it is inexpensive, off-patent, produced in large quantities in India and is being exported to 55 countries and evoked global attention after it was endorsed by U.S. President Donald Trump and gained emergency use authorisation by the United States Food and Drug Administration.

 

Two trials in patients — again, not RCTs and in small groups — in France and South Korea found that teh drug reduced viral loads as well as protected hospitalised patients and healthcare workers exposed to the virus and appear to be prime source of optimism about its prophylactic potency.

On the other hand, it has also been linked to retinopathy and cardiac malfunction which is why it evokes deep scepticism among doctors and medical experts on India’s faith in the drug.

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“We know that HCQ has been used for over four decades for immuno-modulation in immune disorders such as rheumatoid arthritis, lupus erythematosus etc. Some patients have been on lifelong therapy of one tablet every day. Armed forces have used quinine for protection from malaria for years. The reason some people are now talking against HCQS is the “potential serious side effects” of this drug. Of special concern is it’s effect on the heart. But the fact of the matter is that this drug is extremely safe and side effects are mild and extremely rare and are being blown out of proportion in today’s scenario. Of course, if somebody already has an underlying cardiac problem, one has to be extremely careful in giving this drug,” said Dr. Yash Gulati, orthopedic surgeon, Indraprastha Apollo Hospitals, New Delhi.

Joint Secretary in the Ministry of Health Lav Agarwal said the recovery rate for COVID-19 cases in the country has seen an upwards trend.

The recovery rate in the country continues to improve and is presently 41.61%. The COVID-19 fatality rate has reduced from 3.3% on April 15 to 2.87% which is among the lowest in the world,” he said