Explaining the outcome of India’s largest study on Tocilizumab which was conducted from May to October 2020, the National Lead investigator and Chairman of the Medanta Liver Institute, Dr Arvinder Soin said that this was the first Phase 3 study to demonstrate that while routine use of TCZ on all hospitalized COVID patients was not warranted, TCZ improved survival among patients with severe COVID-19.
Eleven well known public and private tertiary care hospitals from 10 Indian cities participated in the study. A total of 180 patients were recruited, 90 of whom received Tocilizumab (TCZ) and standard care, whereas the other 90 received only standard care. Steroids and Remdesivir once allowed by the MoHFW, were administered to patients in both arms.
While there was no difference in mortality and need for ventilation among the two groups of patients when moderate and severe categories of patients were considered together, a subgroup analysis of the severe patients in the two groups showed a lower mortality (8/50; 16%) among those who received Tocilizumab compared to those who did not (14/41; 34%) at 28 days. TCZ was shown to be safe as the reported adverse events did not differ between the TCZ and standard care arms, said Dr. Soin.
Elaborating on the use of TCZ, Dr Soin said given the conflicting results of the previous studies, millions were wasted last year on indiscriminate use of TCZ, since the exact stage of the disease in which to use the drug was not clear. COVID is not going away any time soon. So, this study plugs an important gap in knowledge on COVID treatment and gives a clear direction on the timing of TCZ in COVID treatment.
Incidentally, in the last month, two major studies - the RECOVERY Trial from UK and the REMAP-CAP study - have revealed similar findings, that TCZ reduces mortality among patients with severe COVID. However, unlike our study, these are not yet published in peer-reviewed journals. Prompted by these findings, the NHS in the UK have now included TCZ as part of their standard treatment protocol of patients with severe COVID, Dr Soin said.
In their paper, the COVINTOC team of investigators, have also brought out the difficulties encountered in conducting trials during the pandemic. They were impeded by challenges such as changing standard care, administration of off-label treatments, rapidly evolving understanding of pathogenesis and treatment, multiple trials competing for participants, media hype, and the publication of non-peer reviewed reports.
Additional barriers included low research fund allocation, deficiencies in drug availability, logistical challenges, travel restrictions, reluctance or inability of patients who have recovered from COVID-19 to travel back to sites for follow-up visits, and shortages in research staff because the risk for contracting SARS-CoV-2 is high and personnel are deployed for active clinical care in already over-stretched systems.
Congratulating the multi-institutional Indian research team, Dr Naresh Trehan, Managing Trustee of the Medanta Institute of Education and Research, and Chairman & Managing Director, Medanta, said, “This research is instrumental in giving the medical fraternity clarity on when to use TCZ in COVID. Becoming the first ones to provide published evidence of this to the world, we have demonstrated that, even during a pandemic, it is possible to conduct a randomised controlled trial despite the multiple challenges and constraints encountered.” (UNI)