Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
Budha O Singh, Bikram Moirangthem, Prasan Kumar Panda, Yogesh Arvind Bahurupi, Sarama Saha, Girraj Saini, Minakshi Dhar, Mukesh Bairwa, Venkatesh Srinivasa Pai, Ankit Agarwal, Girish Sindhwani, Shailendra Handu, Ravikant
doi:10.1101/2021.06.06.21258091
Background Definitive antiviral treatment is not available for COVID-19 infection except remdesivir that even with many doubts. Various combination antivirals have been tried.
Methods A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in COVID-19. Enrolled patients in severe category were randomized into three groups: A: standard treatment, B: hydroxychloroquine+ribavirin+standard treatment, or C: lopinavir+ritonavir+ribavirin+standard treatment; while non-severe category into two groups: A: standard treatment or B: hydroxychloroquine+ribavirin. Combination antivirals was given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report.
Results Total 111 patients randomized: 24, 23, and 24 in severe category A, B, and C respectively, and 20 in each non-severe group. Two patients receiving ribavirin experienced drug induced liver injury and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups respectively showed symptomatic recovery compared to 93.3% and 86.7% in A and B groups respectively in the non-severe category at 72hrs (P>0.05).
Conclusions The results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19. However, results do indicate the benefit of non-standard interventional combination therapy in severe disease. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.
Given the results of the findings of the study and availability of a variety of therapeutic approaches including novel antivirals, modifiers of the immune response, or other intrinsic pathways, antiviral combinations may have a role in improving clinical recovery in patients of COVID-19 with severe category whereas only standard therapy is required for non-severe category. Competing interests: The authors declare that they have no competing interests.
Trial registration: Funding: Non-funded. Authors' contributions: PKP conceived the trial. PKP, AB, BCS, GC, YAB designed the trial. BCS, BM, SS collected the data. All the authors are part of the trial management committee and were involved in the review, amendments, and approval of the final protocol.
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