A decision to pause the trial was taken three weeks ago when an interim analysis of data showed higher deaths in the group receiving the plasma. The investigators also found the possibility of the plasma increasing thrombotic tendency (clotting of blood inside the vessel) in the recipients. The trial was being carried out across the state’s 21 medical colleges, and around 150 participants had been recruited so far. Of these, at least half had received plasma.
“Deaths seemed to be more in the plasma arm (group), although not significantly higher than the placebo arm. Still experts thought it was best to stop the trial and understand if the plasma or severity of disease itself was responsible. We didn’t observe any real benefits,” said one of the investigators who didn’t wish to be named. The researchers had shared interim observations with the Data and Safety Monitoring Board (DSMB), an independent group of experts monitoring safety and efficacy in any ongoing trial. “Our DSMB experts recommended the trial be put on hold till all available data was analysed,” another doctor added. One of the city doctors said they also struggled to recruit as the number of critical patients began to drop significantly.
The trial was part of the larger ‘Project Platina’ launched by the state in June last year, when plasma was being hailed as a magic bullet for treatment of Covid. The trial was to be conducted in critical patients, while plasma was also to be given for emergency off-label use to other patients. A budget of Rs 16 crore was sanctioned to facilitate the trial. A state official confirmed that while the trial has been put on hold, plasma for the off-label category will continue to be dispensed. Nearly 1,000 patients have received plasma under the off-label part of the project.
One investigator said they also considered data from similar trials being carried out globally. A study published by researchers from Argentina in the New England Journal of Medicine in November found no significant differences in clinical status or overall mortality where plasma was given to 228 patients and placebo to 105. The 30-day mortality was 10.9% in the plasma group and 11.4% in the placebo group. India’s first major plasma trial by ICMR on moderate patients too had found it did not reduce mortality or progression to severe Covid. “One of the fundamentals of clinical trials is to stop if the product or agent studied is suspected to be harmful,” the investigator said.
Dr Shashank Joshi, a member of the state task force, said use of plasma and other experimental drugs has reduced and is largely on a case-to-case basis.