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Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19

Panda et al., Clinical Pharmacology: Advances and Applications, doi:10.2147/CPAA.S325083, CTRI/2020/06/025575
Sep 2021  
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Mortality 48% Improvement Relative Risk HCQ  Panda et al.  LATE TREATMENT  RCT Is late treatment with HCQ + ribavirin beneficial for COVID-19? RCT 41 patients in India (June 2020 - May 2021) Lower mortality with HCQ + ribavirin (not stat. sig., p=0.45) Panda et al., Clinical Pharmacology: A.., Sep 2021 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
RCT 111 patients in India in 5 groups: severe patients: a) standard treatment, b) hydroxychloroquine + ribavirin + standard treatment, or c) lopinavir + ritonavir + ribavirin + standard treatment, and non-severe: a) standard treatment or b) hydroxychloroquine + ribavirin. Non-severe patients were transferred to the severe group on progression.
risk of death, 47.5% lower, RR 0.53, p = 0.45, treatment 3 of 20 (15.0%), control 6 of 21 (28.6%), NNT 7.4.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Panda et al., 30 Sep 2021, Randomized Controlled Trial, India, peer-reviewed, 13 authors, study period June 2020 - May 2021, this trial uses multiple treatments in the treatment arm (combined with ribavirin) - results of individual treatments may vary, trial CTRI/2020/06/025575. Contact:
This PaperHCQAll
Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19
Prasan Kumar Panda, Budha O Singh, Bikram Moirangthem, Yogesh Arvind Bahurupi, Sarama Saha, Girraj Saini, Minakshi Dhar, Mukesh Bairwa, Venkatesh Srinivasa Pai Pai, Ankit Agarwal, Girish Sindhwani, Shailendra Handu, Ravi Kant
Clinical Pharmacology: Advances and Applications, doi:10.2147/cpaa.s325083
Purpose: Definitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combination therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in mild-severe COVID-19. Patients and Methods: A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir +ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were 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: In total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. 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 72 hours (P>0.05). Conclusion: Though 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 due to very small sized trial, clinically hydroxychloroquine+ribavirin therapy is showing better recovery by 7.4% than standard therapy in the former category. However, results do indicate the benefit of standard therapy in the non-severe category by 6.6%. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.
Ethics Statement All participants were informed about the purpose of the trial, consented, and the trial was conducted in accordance with the Declaration of Helsinki. Author Contributions All authors made substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. Disclosure The authors report no conflicts of interest in this work.
Accessed, None
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Late treatment
is less effective
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