The Gujarat Food and Drug Control Administration (FDCA) has asked the Drugs Controller General of India (DCGI) and Indian Council of Medical Research (ICMR) to encourage use of convalescent plasma (CP) therapy in C-19 patients.
This is the following evidence based advisory of ICMR issued to the stakeholders to address inappropriate use of convalescent plasma in C-19 patients.
“Government of Gujarat through Gujarat FDCA was the first to get the CP therapy protocol and guidelines in the country from DCGI and ICMR early in the month of April 2020. It also has the distinction of being the first state to treat patients through CP therapy in the month of April 2020.
During the lockdown, we fast tracked approvals in consultation with the DCGI to set up 16 plasma banks which are today completely functional and working towards patient safety. CP therapy needs to be encouraged in the absence of an efficacious vaccine which is still work in progress,” informed Gujarat FDCA Commissioner Dr H G Koshia.
As of today, Gujarat has 146 blood banks across the state.
Maharashtra has been struggling to keep its plasma banks functional due to price control issues between the state government and plasma banks.
Meanwhile, the Central Government has also been considering removing CP therapy from the national clinical management protocol for C-19. However, clinicians have contested that clinical trial studies to prove the efficacy of CP therapy are still ongoing and need some more time to arrive at the right conclusion in the interest of patient safety.
As per the ICMR advisory, Convalescent Plasma Therapy (CPT) or passive immunotherapy has been tried in the past for treatment of viral infections like H1N11, Ebola and SARS-CoV-13 etc. Benefits of CPT in improving the clinical outcomes, reducing severity of disease, duration of hospitalization and mortality in C-19 patients are dependent on the concentration of specific antibodies in convalescent plasma that could neutralize the effects of SARS-CoV-2.
ICMR conducted an open label phase II multicentre randomised controlled trial in India across 39 public and private hospitals on use of convalescent plasma in the management of cases with moderate C-19 disease (PLACID Trial). It was concluded that CPT did not lead to reduction in progression to severe C-19 OR all-cause mortality in the group that received CPT as compared to the group that did not receive CPT.
PLACID is the world’s largest pragmatic trial on CPT conducted in 464 moderately ill laboratory confirmed C-19 affected adults in a real world setting wherein no benefit of use of CPT could be established.
Similar studies conducted in China and Netherlands have also documented no significant benefit of CPT in improving the clinical outcomes of hospitalised C-19 patients.
As per the ICMR advisory, indiscriminate use of CPT is not advisable. It is speculated that convalescent plasma having low concentration of specific antibodies against SARS-CoV-2 may be less beneficial for treating C-19 patients as compared to plasma with high concentration of such antibodies. This advisory therefore embraces the principle that a potential donor for convalescent plasma should have sufficient concentration of antibody working against C-19 as narrated in the matrix below. It also highlights that presence of antibody against C-19 in a potential recipient makes transfusing convalescent plasma a futile intervention.
CPT therefore should only be used, as advised by ICMR for management of C-19 when specific criteria as mentioned are met. The Appropriate age for CP donation is between 18 and 65 year three to seven days from onset of symptoms but not later than 10 days. There should be screening to rule out ABO incompatibility and blood borne pathogens such as HIV, HBV, HCV etc. There should be required concentration of IgG antibody against C-19 Titre of 1:640 (ELISA) or 13 AU (Absorbance Unit)/mL9 (CLIA) or Neutralising Antibody Titres of 1:80 (PRNT/MNT), as per the advisory.