Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.
Right now there is still no approved treatment for COVID-19, although several possible drugs and novel agents, which have not been clinically tested, are available through compassionate use which is still in trial stage. Convalescent plasma (CP) is also considered as one of the therapies for patients with COVID-19, which is also in trial stage. Convalescent plasma therapy involves the use of antibodies from the blood of patients who have recovered from COVID-19 to treat infected patients. In a small case series involving five critically ill COVID-19 patients with ARDS, infusion of convalescent plasma with neutralising antibodies led to improvement in clinical status in all patients without any deaths. In another small series of four patients, including one pregnant woman, all four recovered eventually.
Also convalescent plasma was historically used in viral diseases, such as poliomyelitis, measles, mumps and influenza, before vaccines were developed. It has also shown some success as a neutralizing antibody against other corona virus epidemics, SARS-1 and Middle East respiratory syndrome (MERS), in the first two decades of the 2000s. CP-derived antibodies can neutralize a virus by preventing replication (e.g., by complement activation or phagocytosis) or by binding without interfering with replication. 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 in contrast to the cavalier manner in which it approved the anti-malarial hydroxychloroquine, as a prophylaxis for corona virus without carrying out any trial and relying on evidence that was slim and intended only for treatment, and also when the risks were unknown. If the trial outcomes are overwhelmingly positive, the agency would be ethically obliged to recommend plasma therapy as a standard of care for COVID-19 patients.
The trial will be conducted as an open label, randomised, controlled Phase II study to evaluate the safety and efficacy of convalescent plasma in patients with moderate COVID-19 infection. The primary outcome to be measured is a composite of avoidance of progression to severe ARDS (P/F ratio) or all-cause mortality at 28 days. Plan is to enrol 452 patients of moderate COVID-19 patients over next 6 months. The adverse events related to plasma transfusion will be regularly monitored.