A day after the World Health Organisation (WHO) suspended the allocation of patients in the hydroxychloroquine (HCQ) arm of its multi-country Solidarity Trial to find an effective treatment for Covid-19, India reiterated its faith in the continued prophylactic use of the anti-malaria drug for the novel coronavirus disease.
There is enough experience in the country of using HCQ, and sufficient data from observational and case control studies to warrant its use, the government said.
HCQ also continues to be used for treatment of Covid-19, along with the antibiotic azithromycin. “We will review it,” Dr Balram Bhargava, DG, Indian Council of Medical Research (ICMR) and Secretary, Department of Health Research, said on Tuesday.
Dr Vinod Paul, Member (Health) at NITI Aayog, and chairman of the Empowered Group on the government’s medical emergency management plan, said: “We have used chloroquine for years. My teacher used to say that when a child comes with fever give chloroquine and wait for three days. HCQ is even more safe because it is used continuously in rheumatoid arthritis. There is valid biological plausibility for its use. It is known to increase the pH of the cell and make it alkaline. Along with zinc it blocks the entry of the virus into the cell. Admittedly this is a new virus whose behaviour we are still learning about, but it (HCQ) is known to work in other coronaviruses. We have taken a call based on biological plausibility and availability of the drug.”
Dr Paul said that the evidence had been examined “very thoroughly, including before making the expanded recommendation [for prophylactic use of HCQ] last week for all frontline workers”, including those not in healthcare.
“Collectively the academic and research fraternity of India has put its faith in the drug. Prima facie there is a case for use of the drug. We will modify and expand the protocol as we go along, use it both for therapy and prophylaxis. There are minimal and tolerable side effects of HCQ including abnormal ECG and arrhythmias. However for the purposes for which we are recommending it, the benefits far outweigh the risks,” Dr Paul said.
Jury is still out
As ICMR’s Dr Balram Bhargava says, we don’t know for sure what drug is working and what isn't in the fight against the novel coronavirus. Chloroquine has been in use for a century, and HCQ is considered a safe drug. The WHO has said that a call on HCQ would be taken after a review of the existing evidence, some time in the middle of next month.
Dr Bhargava agreed with Dr Paul. Replying to a question at Tuesday’s Covid-19 briefing, he said: “This is a new virus. We don’t know what drug is working or what is not. There are a lot of drugs being repurposed for treatment or prophylaxis. Chloroquine is in use for 100 years. HCQ is even safer…
“The biological plausibility showed it could be an antiviral drug. There was data published in [the journal] Nature etc., that it showed antiviral activity. We found similar properties in vitro. American government started using it, got fast-track approval. We had thought it may be a useful drug for prophylaxis based on in vitro data, bio plausibility and availability and safety of the drug. We had recommended it for empiric use under strict supervision some time back. During these six weeks we got some data in India and they were mainly observational studies, some were case control studies at AIIMS and ICMR and three public hospitals in Delhi. It was difficult to do RCT [randomised controlled trial] of something that we say “may benefit”. We looked at data from both kinds of studies and found that it may be working,” he said.
No major side effects except nausea and occasionally some palpitation were detected, Dr Bhargava said
“In the advisory we have written for prophylaxis it should be continued because there is no harm, and benefit may be there… Secondly, we found side effects, so said it should be taken with food. Third was, we need to do one ECG during use of the drug. We expanded recommendations from healthcare to frontline workers for eight weeks or beyond once there is an ECG available and it is safe. Looking at risk-benefit, we found that possibly we should not deny our frontline or healthcare workers dealing with Covid,” he said.
Several private hospitals in Mumbai have, however, stopped using HCQ to treat patients of Covid-19.
Doctors in these hospitals said they had observed adverse reactions in a few patients who were being given a combination of HCQ and azithromycin.
Government hospitals in Mumbai, however, continue to use the drug for patients showing mild to moderate symptoms.
Explained | Hydroxychloroquine use in worst-hit Maharashtra
The number of cases in India reached 1,45,380 on Tuesday, with 6,535 new cases being reported in the last 24 hours. A total 4,167 people have died from the disease – however, an analysis of case mortality shows that India has had about 0.3 deaths per lakh population, which is amongst the lowest in the world. Globally, the mortality rate is 4.4 deaths per lakh population.
Pulmonologist Dr Jalil Parkar, who has been treating severely ill Covid-19 patients in Lilavati Hospital, said: “A few patients showed QT prolongation. We decided to change the regimen because this drug was not found effective.”
QT prolongation refers to chaotic heartbeats, which show up in a patient’s electrocardiogram. Dr Parkar said he had stopped using HCQ even before the WHO suspended its trial, and had switched to a regimen of ivermectin and doxycycline instead.
Dr Gunjan Chanchalani, chief intensivist at Bhatia Hospital, said, “We have not seen adverse reaction yet, but we reduced its (HCQ) use to very few patients after so many negative reports. Now we plan to completely stop using HCQ.”
In Nanavati Hospital, Dr Rahul Tambe said they were not using HCQ for hypertensive, diabetic, and cardiac patients, and elderly patients. “It is being used for a very limited number of patients. We still need more data on it.”
Dr Balkrishna Adsul, in-charge of Seven Hills Hospital, said they had noticed adverse reaction in a few patients with renal complications. “But we will continue to administer the drug until the ICMR guidelines change. Every drug has some side effects,” Dr Adsul said.
The current protocol at hospitals run by the Brihanmumbai Municipal Corporation (BMC) is based on ICMR guidelines, which recommend HCQ for mildly or moderately ill patients, as well as patients with pneumonia, respiratory failure, and organ dysfunction for at least nine days. The doses are small, ranging from 200 mg to 400 mg, and are being given mainly to patients between ages 15 and 40.
Dr Subhash Salunke, technical advisor to the state government, said that since the WHO has only paused – and not stopped – the HCQ trial, Maharashtra would for now continue to administer the drug to patients.
“We should not jump to conclusions. We need to take ECG, and observe patients closely for the effect of the drug. It should not trigger panic,” Dr Salunke said.
Health Secretary Dr Pradeep Awate said: “ICMR released data which has shown only three serious side effects of HCQ as a prophylactic till now. WHO’s Solidarity Trial used double the dosage that ICMR prescribes for its patients. Since our dosage is small, we are not concerned about side effects,”
On Monday, the WHO said that a call on HCQ would be taken after a review of the existing evidence, some time in the middle of next month.
WHO Chief Scientist Dr Soumya Swaminathan told The Indian Express on Tuesday that this was a temporary step, which will be reviewed based on evidence emerging from various trials worldwide, as well as published research.
“There is no need for panic, but randomised trials need to be conducted on the use of the drug for prophylaxis,” Dr Swaminathan said. “The safety profile of the drug needs to be studied in both cases – drugs given to hospitalised patients and to healthy individuals exposed to Covid-19.”
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