New Delhi: The Indian Council of Medical Research (ICMR)’s advisory on the usage of anti-malarial drug hydroxychloroquine (HCQ) as a preventive drug created a row last week, with a Lancet study seemingly contradicting its position. But there is a clear and nuanced distinction in the scope between the two.
On 22 May, a study published in the medical journal said HCQ increases the chances of death and irregular heart rhythm. Titled Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, the study was conducted on over 96,000 hospitalised Covid-19 patients across six continents.
On the same day, India’s apex research body released an advisory to expand the usage of HCQ as a preventive drug, or prophylaxis, for Covid-19. This was based on three observational studies the research body has conducted.
But unlike The Lancet study, the ICMR only investigated if frontline healthcare workers, who were given the drug as prophylaxis, contracted the disease or not.
ThePrint analysed the ICMR’s guidelines and The Lancet study to understand how the two studies differ in their scope and what we know of the effects of HCQ on Covid-19.
What The Lancet study found
The Lancet study is the largest observation research to be conducted on the use of HCQ and its predecessor chloroquine as a treatment for Covid-19.
A majority of the previous studies, which spurred the existing perception about the efficacy and safety of HCQ, were small uncontrolled studies.
In India, only five trials have been registered to test the drug’s efficacy and safety, according to ICMR’s Clinical Trial Registry of India (CTRI). Of these, the biggest is the World Health Organization’s Solidarity Trial, with 7,000 participants from across countries. It started recruiting patients earlier this month, according to CTRI.
The Lancet study by four researchers from the US and Switzerland was “a multinational registry analysis” of health records of patients from as many as 671 hospitals from all over the world.
The analysis included data of the patient’s age, body-mass index, sex, race or ethnicity and their underlying comorbidities. The 96,032 Covid-19 patients who were included in the study had been hospitalised between 20 December 2019 and 14 April.
Of them, four groups of 14,888 patients received each one of these four treatments —chloroquine, chloroquine with a macrolide (an anti-bacterial drug that works by inhibiting protein synthesis of the pathogen), hydroxychloroquine, and HCQ with a macrolide.
A fifth group served as the control group that received no therapy.
“When compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%), hydroxychloroquine with a macrolide (23·8%), chloroquine (16·4%), and chloroquine with a macrolide (22·2%) were each independently associated with an increased risk of in-hospital mortality,” the study said.
Moreover, arrhythmia or irregular heartbeat was observed in only 0.3 per cent of the control group, this was seen in 6.1 per cent of those receiving HCQ, 8.1 per cent of the group receiving HCQ and a macrolide, 6.5 per cent of those being treated with chloroquine and a macrolide and 4.3 per cent of those who were just given chloroquine.
“These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed,” concluded the study.
How is it different from ICMR’s studies?
The three studies by ICMR — based on which it put out the advisory Friday — differed in its scope as it only checked if HCQ worked as a preventive drug.
Of the three, one was an observational study of 334 healthcare workers at New Delhi’s All India Institute of Medical Sciences (AIIMS); a retrospective case control study by ICMR based on previously collected data; and an investigation in three central government hospitals.
All three indicated that healthcare workers who had taken HCQ were less prone to Covid-19, according to ICMR’s advisory.
The research body, however, has not released data from the studies or made the actual studies public.
The apex health research body also referred to an in-vitro (laboratory) study conducted by the National Institute of Virology in Pune that “showed reduction of infectivity/log reduction in viral RNA copy of SARS-Cov2” (Covid-19’s viral genome).
Multiple in-vitro studies have shown positive effects in fighting the virus in many countries, but there have been no studies confirming that this translates to human bodies yet.
‘Protecting, even with side-effects’
Dr Rajnikant Srivastava, head of department of research management, policy planning and communication at the ICMR in New Delhi noted this difference between the international study and the ones by ICMR.
“Day before yesterday (on Friday) we released guidelines based on observational studies only checking the use of HCQ as prophylaxis. For Covid-19 treatment, we don’t have any evidence yet from the WHO Solidarity Trial. Once the clinical trial data comes out only will we be able to say anything,” he said.
“Even in our observational studies we’ve shown that there are certain side effects, even then it is protecting against Covid-19.”
In its guidelines, the ICMR says an electrocardiogram test or ECG test, which checks for the heart rhythms, may be conducted when prescribing the drug, and should be conducted in cases where the individual develops cardiovascular symptoms.
“One ECG should be done anytime during the course of the prophylaxis,” the guidelines say.
The ICMR guidelines also add that HCQ can be administered only by a medical professional, and informed consent – where the person being given the drug is aware of its side effects – must be sought before administering it.
‘Won’t change anything without more evidence’
While the US Food and Drug Administration has cautioned against the use of HCQ to treat Covid-19 patients, the treatment guidelines in India state that HCQ and azithromycin, a macrolide, “may be considered as an off-label indication in patients with severe disease and requiring ICU management”. This means that this medication may be used in a manner not specified in the guidelines.
According to ICMR’s Revised Guidelines on Clinical Management of COVID–19, the Covid-19 patient can be administered 400 mg of HCQ for one day and then 200 mg for four days along with 500 mg of azithromycin.
Asked if the government would reconsider these treatment protocols in view of The Lancet study, Srivastava said, “Unless and until there is more evidence we will not change anything.”
ThePrint also reached AIIMS director Randeep Guleria, who is a member of the National Covid Task Force, through phone calls, but there was no response until the time of publishing this report.