Treatment of critically ill coronavirus patients with an experimental antiviral drug did not reduce deaths, a trial has found.
The first randomised control trial of remdesivir involving 237 adults from 10 hospitals in Wuhan, China, found that the drug did not speed recovery or reduce deaths from Covid-19 compared with placebo in hospitalised patients.
But because the study, published in The Lancet on Wednesday, was stopped early the true effectiveness of remdesivir remains unclear, authors said.
Professor Bin Cao from China-Japan Friendship Hospital and Capital Medical University in China, who led the research, said it was not the outcome his team hoped for.
He added: “Unfortunately, our trial found that while safe and adequately tolerated, remdesivir did not provide significant benefits over placebo.
“This is not the outcome we hoped for, but we are mindful that we were only able to enrol 237 of the target 453 patients because the Covid-19 outbreak was brought under control in Wuhan.
“What’s more, restrictions on bed availability resulted in most patients being enrolled later in the disease course, so we were unable to adequately assess whether earlier treatment with remdesivir might have provided clinical benefit.”
The data safety monitoring board stopped the trial because researchers were unable to recruit enough patients following the steep decline of cases in China.
Future studies need to determine whether earlier treatment with remdesivir, higher doses, or combination with other antivirals or SARS-CoV-2 neutralising antibodies, might be more effective in those with severe illnessProfessor Bin Cao
The authors said that due to this more evidence was needed to establish if remdesivir can provide a “meaningful clinical benefit”.
Prof Bin Cao said: “Future studies need to determine whether earlier treatment with remdesivir, higher doses, or combination with other antivirals or SARS-CoV-2 neutralising antibodies, might be more effective in those with severe illness.”
Remdesivir, which was originally developed to treat Ebola, is one of a handful of experimental drugs undergoing clinical trials worldwide to treat coronavirus.
The study said that it had been shown to successfully block Covid-19 from replicating in vitro, and had activity against other coronavirus infections like Sars, Mers, and Covid-19 in animal studies.
Case studies have also reported benefit in some severely ill patients with Covid-19, but there had been no clinical trials of remdesivir, they added.
All the patients had to enter the study within 12 days of symptom onset, have pneumonia confirmed by chest imaging, and oxygen saturation of 94% or lower.
Participants were randomly assigned to either daily infusions of remdesivir or placebo infusions then, over 28 days, trained investigators measured the time to clinical improvement.
The study found no statistically “significant difference” in time to clinical improvement between the groups with the average time 21 days for the remdesivir group and 23 days for the placebo group.
Death within 28 days of randomisation was also similar between the groups, with 14% of patients dying in the remdesivir group compared with 13% in the placebo group, it found.
However, the authors said that although not statistically significant patients treated within 10 days of illness onset with remdesivir appeared to recover faster than those given placebo – 18 days compared to 23.
Patients treated with remdesivir within 10 days of illness onset also had a lower – but again not statistically significant difference – in mortality, 11% compared to 15% of the placebo group.
The duration of invasive mechanical ventilation, although again not significantly different between the groups, was shorter in remdesivir recipients than placebo recipients at an average of seven days compared to 15-and-a-half days.
The study found that there was no difference in adverse events between the groups but more patients in the remdesivir group discontinued treatment because of adverse events including gastrointestinal symptoms such as nausea and vomiting and cardiopulmonary failure – 12% compared to 5%.
Trudie Lang, professor of global health research at the university of Oxford, said the study being stopped showed the “limited window” of when there were enough patients needed to carry out clinical research.
She added: “Many questions remain about our understanding of Covid-19, and we still need to evaluate drugs and vaccines.
“The whole world will benefit from answering these questions across all populations and different settings.
“It is a global pandemic and we need to ensure global equity in who benefits from the evidence and treatments that are developed.”