Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial

PLoS One. 2023 Mar 16;18(3):e0282688. doi: 10.1371/journal.pone.0282688. eCollection 2023.

Abstract

Objective: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19.

Methods: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched.

Results: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome).

Conclusions: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required.

Trial registration: CTRI/2020/06/025557.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • COVID-19 Drug Treatment* / methods
  • Drug Therapy, Combination / adverse effects
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Phytotherapy*
  • Severity of Illness Index
  • Standard of Care
  • Treatment Outcome

Substances

  • Ayush 64

Associated data

  • CTRI/CTRI/2020/06/025557

Grants and funding

The current study was sponsored by Central Council of Research in Ayurvedic Sciences (CCRAS), Ministry of AYUSH, Government of India. CCRAS authorized the study grant vide their Order Reference F.No.3-61/2020-CCRAS/Admn/IMR/458 dated 02 June 2020 (CCRAS website: http://www.ccras.nic.in). The grant was distributed and supervised by the authorized CCRAS officer to the 3 CCRAS run study sites. No individual was paid any part of the research grant. CCRAS selected the principal investigators from the study sites. The PIs selected the study site staff who were paid salary/compensation from the site grant as a-priori approved by the CCRAS. CCRAS also appointed a 'Contract research organization (CRO)' on contract payment to supervise and co-ordinate the trial as per the Government policy. CCRAS did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. AYUSH 64, the investigational product in this study, was a proprietary formulation of CCRAS and directly (central procurement) supplied to the study sites. None of the authors received any funding for participation in the current study project. Amongst the authors, KC, GR, AS, ML,DG,HR, MG, BCSR, BY, NS were Ayurvedic physician investigators and salaried employees of CCRAS run Government medical institutions. ST was paid by the CRO. AR and GT were Ayurvedic physician consultants and AR was paid a honorarium by the CCRAS. AC was a rheumatologist in practise and appointed as the Chief Clinical Coordinator of AYUSH CSIR Project (research drug trials in COVID-19). BP was the Chairman, Interdisciplinary AYUSH R & D Task Force on COVID-19 set up Ministry of AYUSH, Government of India. MS was a research coordinator and assisted AC. AC, MS and BP worked in a voluntary capacity and did not receive any remuneration from CCRAS.