ICMR’s insistence on an evidence-based approach to plasma therapy is a welcome change and is in stark contrast to the cavalier manner in which it approved hydroxychloroquine as a prophylaxis for coronavirus without carrying out any trial and relying on evidence which was slim and dodgy and that too only for treatment, and also when the risks were unknown.
With the ethics committee approval in hand on May 8, the Indian Council of Medical Research cleared the last hurdle to conduct a multicentric phase-2 trial using convalescent plasma on COVID-19 patients with moderate illness. Three feasibility studies carried out by ICMR in about 20 severely ill patients found convalescent plasma therapy to be safe and able to resolve illness or improve the clinical symptoms.
Primary, secondary outcomes
Since safety of convalescent plasma obtained from people who have recovered from COVID-19 illness is not a huge concern, the first stage of human clinical trial has been skipped and ICMR will instead study the safety and efficacy of convalescent plasma in a phase-2 trial involving 452 patients.
The patients with moderate COVID-19 illness will be randomly assigned to receive either convalescent plasma (226 participants) or only standard of care (control group). The trial will be carried out in 21 hospitals spread across the country. The primary outcomes that will be studied in the trial include prevention of illness from progressing to a severe form and avoidance of deaths from all causes at 28 days after plasma infusion.
Some of the important secondary outcomes that will be measured include resolution of symptoms such as fever, shortness of breath and fatigue, and reduction in the duration of hospital stay and respiratory support.
Plasma will be collected from willing donors 28 days after they make a complete recovery from illness or being symptom-free and have the more than the required level of antibodies against the novel coronavirus. Molecular tests will be carried out to ascertain the absence of coronavirus infection and other routine tests performed before the plasma is used.
Convalescent plasma therapy is century old and has shown some benefit in treating measles, chickenpox and rabies. Small studies have shown faster clearance of virus in the case of MERS and SARS if given early in the course of the disease but no randomised controlled studies have been carried out. However, no benefit was seen in 2015 when 84 Ebola patients were treated with convalescent plasma in Guinea.
Only three small studies involving 21 COVID-19 patients have been carried out but not in trials were the participants were randomised with a control arm. Till date, there is a dearth of randomised controlled trails that clearly demonstrate the efficacy of convalescent plasma therapy for any infectious disease, including COVID-19.
Even in the absence of any effective treatment or a vaccine, the current pandemic provides an ideal opportunity to ascertain the clinical benefits of plasma therapy through randomised controlled trials. The U.S. FDA and India have thus approved the use of plasma from recovered COVID-19 patients only for trial purposes.
The ICMR’s insistence on an evidence-based approach to plasma therapy is a welcome change and is in stark contrast to the cavalier manner in which it approved the anti-malaria drug hydroxychloroquine as a prophylaxis for coronavirus without carrying out any trial and relying on evidence which was slim and dodgy and that too only for treatment, and also when the risks were unknown.
If the outcomes of the trial are overwhelmingly positive, the agency would be ethically obliged to recommend plasma therapy as a standard of care for treating COVID-19 patients.