The large, multi-nation ‘Solidarity’ clinical trial coordinated by the World Health Organisation (WHO) to find an effective treatment for the novel coronavirus infection has concluded that four commonly used re-purposed drugs have little or no effect on patients admitted in hospital with Covid-19.
The trial, carried out in 405 hospitals in 30 countries including India, looked at four drugs or their combinations — remdesivir, developed originally to treat Ebola; anti-malaria drug HCQ; ritonavir/lopinavir, licensed for treatment of HIV; and interferon beta 1a, used to treat multiple sclerosis.
Solidarity Trial dampener: What does this mean for the drugs that hopes were pinned on?
“No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation or hospitalisation duration,” the research paper, which is yet to be peer- reviewed, said.
On July 6, WHO had accepted the recommendation of the Solidarity Trial’s International Steering Committee to discontinue the HCQ and lopinavir/ritonavir arms of the trial.
The aim of the trial was to determine whether the four re-purposed drugs could moderately affect in-hospital mortality and whether any effects differed between moderate and severe cases of the disease.
Of the more than 11,000 participants in the trial, 2,750 were given remdesivir; 954 HCQ; 1,411 only lopinavir-ritonavir; and 2,063 interferon. A total 4,088 were not given any drug.
Eight per cent of study participants were already ventilated, 25 per cent had diabetes, and 81 per cent were below the age of 70 years. “No study drug had any definite effect on mortality, either overall or in any subgroup defined by age or ventilation at entry (or other entry characteristics, or geographic region, or corticosteroid use),” the study said.
Also, it said, “…no study drug appreciably reduced initiation of ventilation in those not already ventilated”. The researchers said the trial is still recruiting about 2,000 patients per month, who will be assessed for further treatments, including immune-modulators and specific anti-SARS-CoV-2 monoclonal antibodies.
The study said that narrower confidence intervals would be helpful, particularly for remdesivir, which is part of the national clinical management protocol in India.
“For each of these four re-purposed non-specific antivirals, several thousand patients have now been randomised in various trials. The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomized studies, that any will substantially reduce inpatient mortality, initiation of ventilation, or hospitalisation duration,” the study said.
The death rate ratio (active vs control group) for remdesivir was 0.95 – 301 deaths in the active group of 2,743 against 303 in the control group of 2,708. In the hydroxychloroquine arm, the death rate ratio was 1.19 (104 deaths were reported in the active group of 947 patients as against 84 in the control group of 906); in the lopinavir arm, the death rate ratio was 1 (148 deaths in the active group of 1,399, as against 146 in the control group of 1,372); and in the interferon arm, the death rate ratio was 1.16 (243 deaths in the active group of 2,050; 216 in the control group of 2,050).
India contributed one tenth of the participants in the trial, the Indian Council of Medical Research (ICMR) said in a release. The Indian effort was led by ICMR-National AIDS Research Institute (NARI), Pune, with Dr Sheela Godbole at the helm. The trial comprised 26 actively randomising sites with 937 participants in India, ICMR said.