Drug Controller General permits clinical trial of convalescent plasma in COVID-19 patients

The central drug regulator has given its go-ahead to a proposal by the Indian Council of Medical Research for the clinical trial of convalescent plasma in COVID-19 patients, as per the protocol developed by ICMR. The Drug Controller General of India said ICMR has submitted a list of institutes, which have shown an interest in the trial, to the Central Drugs Standard Control Organisation and they may do so in consultation with the health research body.

"It is to inform that in light of public interest the proposal of ICMR for conducting the said trial has been reviewed through the Subject Expert Committee in its meeting held on April 13 under accelerated approval process in light of the current prevailing situation of COVID-19 and based on the recommendation of the committee. "The CDSCO has conveyed its no objection for conduct of the clinical trial subject to certain amendments in the protocol and various conditions under the Drugs and Clinical Trial Rules 2019," the central drug regulator said in a notice.

The notice underlined that ICMR has developed a protocol for a controlled clinical trial with convalescent plasma in moderate COVID-19 patients which has been reviewed by the committee and the same may also be considered by the applicants as appropriate. In convalescent plasma therapy, antibodies from the blood of patients who have recovered from COVID-19 are used to treat severely infected patients.

The study is aimed at assessing the efficacy of convalescent plasma to limit complications in COVID-19 patients and to evaluate the safety of treatment with anti SARS-CoV-2 plasma in coronavirus-infected patients. The death toll due to COVID-19 rose to 480 and the number of cases in the country climbed to 14,378 on Saturday, according to the Union Health Ministry. The ICMR has already sought participation in a phase-II randomised controlled trial to assess the safety and efficacy of convalescent plasma. Currently, there are no approved treatments for COVID-19.

The management plan is supportive care with supplemental oxygen and mechanical ventilation. Multiple trials are being done across the globe to assess the efficacy of various treatment strategies, the ICMR said. The WHO initiated the "solidarity trial" in several countries to compare the effectiveness of the following regimens against COVID-19: Remdesivir, Lopinavir/Ritonavir, Lopinavir/Ritonavir with interferon beta, and Hydroxychloroquine.

In a clinical trial, Lopinavir/Ritonavir did not demonstrate any benefit over standard of care. The US FDA recently approved convalescent plasma from patients recovered from COVID-19 for the treatment of severe or life-threatening COVID-19 infections. In a small case series, five critically ill novel coronavirus-infected patients with ARDS were treated with convalescent plasma containing neutralizing antibodies. Infusion of plasma was followed by improvement in clinical status in all five patients, with no deaths and the study reported that three patients were discharged, whilst two continued to be stable on mechanical ventilation.

In another small case series of four patients, including one pregnant woman, it was seen that all four recovered eventually, the ICMR said. In another feasibility study of convalescent plasma therapy, 10 severely-ill patients were transfused with 200 ml of convalescent plasma and clinical symptoms rapidly improved in three days. Historically, it has been used in viral diseases such as poliomyelitis, measles, mumps and influenza before vaccines became available, the research body said.

A meta-analysis of 1,703 patients with H1N1 influenza during the Spanish Flu of 1918 suggested that patients who received convalescent plasma had lower mortality. Furthermore, 84 patients with Ebola virus disease who were transfused with convalescent plasma without known levels of neutralizing antibodies did not have a survival benefit. Convalescent plasma was also studied during the previous coronavirus outbreak of SARS in 2002-2004.

In a retrospective study of 80 patients, it was observed that patients who received convalescent plasma before day 14 of illness had better outcomes, defined as early hospital discharge, compared to patients who received it after day 14 of illness. "Considering the lack of efficacious treatments for COVID 19 and the epidemic situation with high mortality rate, the US FDA has approved convalescent plasma for COVID-19 for clinical trials, expanded access and single patient emergency investigational new drugs," the ICMR said.

A majority of the adverse effects associated with plasma transfusion are non-lethal. "We hypothesize that the use of convalescent plasma will improve the clinical outcomes in patients with moderate COVID-19 infection. We designed this phase II, open label, randomized clinical trial with the primary objective to assess the safety and efficacy of the convalescent plasma to limit complications in COVID-19 patients," the ICMR said.