Study Says HCQ Could Harm Patients; ICMR Expands Prophylactic Use
A study published in The Lancet has found the drug to be harmful for COVID-19 patients.
Adding to the controversy surrounding the use of chloroquine or hydroxychloroquine for the treatment of COVID-19 patients, yet another study has found worrying results in hospitalised patients who were given the anti-malarial drug. Almost parallelly, the Indian Council of Medical Research (ICMR) has reiterated the use and safety of the medicine as a prophylactic in its revised advisory issued the same day, causing alarm among experts.
Dr SP Kalantri, Director Professor of Medicine at MGIMS and Medical Superintendent of Kasturba Hospital, Sevagram, Maharashtra, told FIT, “As a physician and a researcher, I am a bit worried and alarmed about ICMR’s decision.”
But before we delve into the reasons why doctors are concerned, let’s look at the evidence from the latest global study, published in The Lancet on 22 May.
The observational study - the largest so far - covered 671 hospitals around the world, and found that the use of HCQ or chloroquine had no benefit on the outcomes in patients when given early after the diagnosis of COVID-19. In fact, a higher risk of death and the development of irregular heart rhythms was observed in seriously ill patients.
Out of over 96,000 patients observed in the hospitals, around 15,000 were treated with HCQ, chloroquine, or a combination of either of these with an antibiotic.
“Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19.”The study authors
Speaking to CNN, Dr Mandeep Mehra, medical director of the Brigham and Women's Hospital Heart and Vascular Center and the lead author of the study, said he would suggest hospitals to stop using these drugs to treat the disease caused by the novel coronavirus.
"Our data has very convincingly shown that across the world in a real-world population that this drug combination, whichever way you slice it or dice it, does not show any evidence of benefit, and in fact, is immutably showing a signal of grave harm," he said.
Earlier, several studies had found the drug to be of no benefit to COVID-19 patients, and concerns about its effects on the heart have been raised since the very moment it became the buzzword for the treatment and prevention of COVID-19, after being advocated by US President Donald Trump. With this observational study, the possibility of harm from the medicine gets strengthened.
The US Food and Drug Administration (FDA) last month issued an advisory saying that hydroxychloroquine has "not been shown to be safe and effective".
As evidence for the medicine’s harm emerges in the treatment of COVID-19 patients, India’s nodal research body has expanded its use as a prophylactic, a development which has aroused concern among experts.
ICMR Reiterates HCQ Use As Prophylactic; Doctors Wary
The ICMR issued a revised advisory on the use of HCQ as prophylaxis for COVID-19 infection the same day as The Lancet study, advising against the use of the drug outside of clinical trials, got published.
This came as a follow-up to its guidelines from 23 March, when it had recommended the use of the medicine to prevent the infection among high-risk people. The approval for the drug had been criticised by experts even then, as FIT had reported earlier. The revised advisory has been substantiated by three observational studies conducted by the research body, which found that the use of the anti-malarial drug HCQ helps prevent the infection.
- An observational study of 334 healthcare workers at AIIMS, out of which 248 took HCQ prophylaxis showed that those taking the drug had a lower incidence of the infection than those not taking it.
- Another investigation from three central government hospitals in New Delhi indicates that amongst healthcare workers involved in COVID-19 care, those on HCQ prophylaxis were less likely to develop the infection. The benefit was less pronounced in healthcare workers caring for a general patient population.
- A retrospective case-control analysis at ICMR found that there is a significant dose-response relationship between the number of prophylactic doses taken and the frequency of occurrence of the infection in symptomatic healthcare workers who were tested for the illness.
In light of these observations, the use of HCQ as a prophylaxis has been recommended for asymptomatic healthcare and frontline workers in COVID and non-COVID hospitals, and asymptomatic contacts of confirmed cases. For the former category, the revised guidelines also permit an extension of the dosage of the medicine beyond the previously stipulated 8 weeks with strict monitoring.
The advisory mentions that the drug must be avoided in certain categories of people, including those with existing cardiac rhythm disorders, children under 15 and pregnant women, among others.
“Rarely the drug causes cardiovascular side effects such as cardiomyopathy and rhythm (heart rate) disorders. In that situation, the drug needs to be discontinued. The drug can rarely cause visual disturbance including blurring of vision which is usually self- limiting and improves on discontinuation of the drug. For the above-cited reasons, the drug has to be given under strict medical supervision with informed consent,” the ICMR added.
While The Lancet study focused on the effects of treating patients who already have the infection - and not on the medicine’s use as a preventive measure - doctors are still sceptical about ICMR’s decision.
Experts On Why the ICMR’s Decision Is Worrying
The scientific community around the world continues to be doubtful about the use of the drug in COVID-19 patients - because of an absence of randomized control trials and any concrete evidence showing its benefits.
Dr Sumit Ray, a critical care specialist in Delhi, told FIT, “The three studies quoted by the ICMR are not available in the public domain. They haven’t been published or peer-reviewed. In the scientific world, if your findings are not available to the public, their value remains low. Other researches are finding HCQ to be counter-productive as a course of treatment. Now even if ICMR claims it is useful as prophylaxis, the need to publish the studies for perusal and review. Only then will they have a scientific basis.”
Should the top medical body of the country be issuing it as a prophylactic based on these relatively smaller observational studies, despite there being evidence of harm coming in from around the world?
Dr Kalantri, in conversation with FIT, said, “The 22 May Lancet study is very meaningful clinically. It looks at two critical outcome measures: in-hospital mortality and the irregularities in the heart rhythm , and finds no benefit from the use of hydroxychloroquine (HCQ) or chloroquine. Instead, it reports significant harm in terms of both increased death rates and abnormal cardiac rhythm. While the study is observational, a limitation of the study, the findings are important because of the large sample size, rigorous statistical methods and clinically meaningful outcome events.”
“I am still unable to understand what made the ICMR neglect this study — published in a highly reputed journal and covering close to hundred-thousand patients. The research body has called the drug safe for prophylactic use, despite evidence that its use could cause fatal complications while treating COVID-19 patients or those at risk of acquiring infection. Its recommendations are based on small observational studies, not available to the public. I feel that the ICMR should share the details of the three studies it is banking on to recommend the use of HCQ - study design, sample size, study population, data collection, outcome measures, statistical methods and generalisability of the study. We need more data, not less.”Dr SP Kalantri
He also adds, “Agreed these are desperate times. But we cannot abandon our scientific and logical reasoning during this tumultuous period. In fact, this is the time when we need science even more than ever. Whatever we do in medicine, must be backed by robust evidence. It’s the foremost principle of medical ethics: Do not harm. When there are clear warnings of harm, how can we downplay them and advocate the use of the drug?”
With a lack of concrete evidence for HCQ’s benefit for the treatment and prevention of COVID-19, and solid concerns emerging about its harm to patients instead, the ICMR’s decision will have to be looked at with scepticism.
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