New Delhi: The multi-country Solidarity trial anchored by the World Health Organization (WHO) has concluded that none of the four repurposed drugs that it examined — remdesivir, hydroxychloroquine (HCQ), lopinavir and interferon — have any benefits on the patients of Covid-19.
The interim findings of the four original drugs have now been reported in a pre-print paper — HCQ and lopinavir were dropped from the trial after the first few months.
India’s current clinical management protocol for Covid advises use of remdesivir as an investigational therapy and HCQ as an off-label repurposed therapy for treatment.
“These Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials,” researchers from the Solidarity trial reported in the pre-print paper on Medrxiv.
The trial continues to test the efficacy of monoclonal antibodies. US President Donald Trump, who has just recovered from Covid, received monoclonal antibodies when he was unwell.
A WHO Covid-19 research forum in February 2020 had recommended evaluation of treatments for the disease through large randomised trials and its expert group had zeroed in on these four drugs to carry out an assessment.
The trial began in March. In 405 hospitals in 30 countries, 11,266 adults were randomised, with 2,750 allocated remdesivir, 954 HCQ, 1,411 lopinavir, 651 interferon plus lopinavir, 1,412 only interferon, and 4,088 no study drug.
Search for effective treatments to continue
Dr K.S. Reddy, president, Public Health Foundation of India, and one of the authors of the trial, said, “SOLIDARITY is the largest multi-country trial estimating the impact of four repurposed drugs on reducing deaths in hospitalised patients of Covid-19, compared to the existing standard of care. The trial arms related to hydroxychloroquine and lopinavir were earlier discontinued when interim analyses showed no benefit.”
He added, “The updated analyses, which presents the largest study so far on Remdesivir shows no impact on reduction in mortality, in the overall patient group compared to prevailing standard of care nor was benefit noted in any patient subset. Interferon too did not demonstrate any benefit in reducing deaths compared to controls.”
Reddy, who is also a member of the executive group of the International Steering Committee of the Solidarity trial, said the search for effective treatment will continue.
“Since the main objective of treatments administered to hospitalised patients is to reduce the risk of death, the search for effective treatments will continue through rigorous evaluation of evidence gathered from large randomised clinical trials. SOLIDARITY will continue to examine other therapeutic interventions which hold promise, such as monoclonal antibodies,” he said.
The Solidarity results are consistent with the conclusions of several other trials on the study drugs, all of whom have returned a negative.
HCQ has also consistently returned a negative in most international trials testing its efficacy as a prophylactic drug. India continues to use it for prophylactic purposes.
“For each of these 4 repurposed non-specific antivirals, several thousand patients have now been randomized 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 Solidarity researchers wrote in the paper.
“Narrower confidence intervals would be helpful (particularly for Remdesivir), but the main need is for better treatments. Solidarity is still recruiting about 2000 patients per month, and efficient factorial designs will allow it to assess further treatments, such as immune-modulators and specific anti-SARS- Cov-2 monoclonal antibodies,” the paper added.