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The first-ever randomised control trial of the anti-viral drug remdesivir done on novel coronavirus disease (COVID-19) positive patients has found no significant improvement in them, according to a paper published in the journal The Lancet on April 29, 2020.
This is in stark contrast with what Gilead Lifesciences, the company manufacturing the drug, reported about its findings the same day.
“Our trial found that intravenous remdesivir did not significantly improve the time to clinical improvement, mortality, or time to clearance of virus in patients with serious COVID-19 compared with placebo,” the researchers in The Lancet paper said.
Placebo refers to the group of patients enrolled for the trial who were given an inactive form of the drug in comparison to those who were given an active form.
In medical parlance, such a trial is called a ‘controlled trial’. It is referred to as ‘random’ because COVID-19 positive patients above 18 years of age were randomly selected.
More significantly, the scientists also say that the patients enrolled in their study were less ill than a previous study on ‘compassionate use’ of the drug. They had already been treated somewhat earlier in their disease cycle.
This should have therefore favoured the positive results for the drug. But what happened was in contrast to their expectations. “Our results did not meet this expectation,” they said.
The compassionate use of a drug is defined as its usage in the event of an outbreak without a clinical trial due to unavailability of any other drug.
Some studies done on COVID-19 patients who were administered this drug as ‘compassionate use’ had given positive results. Therefore, the results of this first clinical trial become all the more important.
The trial found that there was no significant difference between the two groups of patients on the duration of ventilation required for them.
Similarly, those given the active drug showed no difference in length of oxygen support required as compared to the group given the inactive drug. The mortality period was also not different. “A 28-day mortality was similar between the two groups,” the paper said.
It was a multi-centre trial conducted on 237 patients. Around 158 were given remdesivir and the rest received placebo. The trial was done at 10 hospitals in Wuhan (China), the erstwhile epicentre of the outbreak.
Patients were injected with 200 mg remdesivir on day 1, followed by 100 mg on days 2–10 once a day. The Chinese Academy of Medical Sciences led the project. More than 40 researchers from China, UK and the US worked on this trial.
What the drug did do, at the best, was to reduce the improvement time of 5 days.
“Among patients who were treated within 10 days of symptom onset, remdesivir was not a significant factor but was associated with a numerical reduction of five days in median time to clinical improvement,” the paper said.
But there is a serious limitation to the findings.
The number of patients required to assess this could not be achieved because “stringent public health measures used in Wuhan led to marked reductions in new patient presentations in mid-March, and restrictions on hospital bed availability resulted in most patients being enrolled later in the course of disease.”
Therefore, the researchers recommended that ongoing controlled clinical trials should confirm or refute these findings.
There were no significant adverse effects of the drug. However, a higher proportion of remdesivir recipients reported gastrointestinal symptoms (anorexia, nausea, and vomiting), increased level of bilirubin and worsened cardiopulmonary status.
Adverse events were reported in 66 per cent, who were given the active drug and 64 per cent in the other one.
Remdesivir has also been used to treat Ebola patients on compassionate use.
Importantly, this drug had shown positive results against the virus (SARS-CoV-2) in the lab. However, the clinical trials failed to give a result.
This should ring in bells for the agencies, including Indian Council of Medical Research (ICMR), recommending Hydroxychloroquine too.
This is because the anti-malaria drug has given positive results against the virus in the lab but no randomised controlled clinical trial has been conducted on it yet for SARS-CoV-2.
What Gilead claimed
In a press release issued on April 29, the multinational drug manufacturer said there were significant improvements in the COVID-19 patients who were administered this drug.
“Gilead plans to submit the full data for publication in a peer-reviewed journal in the coming weeks. The study demonstrated that patients receiving a 10-day treatment course of remdesivir achieved similar improvement in clinical status compared with those taking a 5-day treatment course,” the statement said.
In India, it had been given to four patients in Jaipur who had shown positive results. The ICMR says it may be an effective drug against the virus.