Coadministration of AYUSH 64 as an adjunct to Standard of Care in mild and moderate COVID-19: A randomised, controlled, multicentric clinical trial

  1. Arvind Chopra
  2. Girish Tillu
  3. Kuldeep Chuadhary
  4. Govind Reddy
  5. Alok Srivastava
  6. Muffazal Lakdawala
  7. Dilip Gode
  8. Himanshu Reddy
  9. Sanjay Tamboli
  10. Manjit Saluja
  11. Sanjeev Sarmukkaddam
  12. Manohar Gundeti
  13. Ashwinikumar Raut
  14. BCS Rao
  15. Babita Yadav
  16. Narayanam Srikanth
  17. Bhushan Patwardhan

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Abstract

Objectives

To compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19.

Design

Multicentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration.

Setting

COVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospital

Participants

140 consenting, eligible, hospitalized adult patients suffering from mild and moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if disease becomes severe.

Interventions

Two tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued till study completion. SOC (symptomatic and supportive) as per national guidelines of India for mild and moderate disease.

Main outcome measures

Time period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocol

Results

140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis. Both groups were matched at baseline. The mean time to CR from randomization was significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion (69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05) superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE) reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related. 22 participants (8 on AYUSH) were withdrawn. No deaths were reported.

Conclusions

AYUSH 64 hastened recovery, reduced hospitalization and improved overall health in mild and moderate COVID-19 when co-administered with SOC under medical supervision. It was safe and well tolerated. Further studies are warranted.

Trial registration

The Clinical Trials Registry India Number CTRI/2020/06/025557

Funding

CCRAS, Ministry of AYUSH, Government of India

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  1. ScreenIT

    SciScore for 10.1101/2021.06.12.21258345: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The protocol was approved by the Institutional Ethics Committee at each study site and registered in the Clinical Trials Registry of India (CTRI) (registration number CTRI/2020/06/025557) prior to patient enrolment (26).
    Consent: Patients: Voluntary hospitalized patients suffering from mild and moderate symptomatic COVID-19 were selected and after signing informed consent were screened for eligibility.
    Sex as a biological variablenot detected.
    RandomizationThis was a prospective, randomized, open label (assessor blind), two arm multicentre study with an exploratory research design and was planned and carried out during the COVID-19 pandemic (May-Nov 2020).
    BlindingAll patients were managed for COVID-19 by an attending physician designated by the hospital at study site and who remained blinded to the treatment allocation in the trial (assessor blind).
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Standard statistical software programs were used (GraphPad InStat Version 3.6 and Confidence Interval Analysis software analysis, BMJ Group, London, 2003).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Undoubtedly, AYUSH 64 can be recommended for use in domiciliary and quarantine setting but with a caveat. It needs to be medically supervised and patients suitably counselled as was done in the current study. It is difficult to predict severe COVID-19 (32). A small proportion of mild cases develop severe disease (32, 33). However, mild and moderate cases may develop post COVID-19 complications (34). Provision of timely critical care in a hospital is a pivotal component for successful management of the pandemic. In our experience, despite sound medical advice, a large proportion of mild and moderate uncomplicated cases are admitted in the hospital and clog the system. AYUSH 64 plus SOC seemed to have significantly reduced the duration of hospitalization. A similar reduction in the length of hospital stay was reported in a meta-analysis of controlled drug trials of co-administration of Chinese herbal medicine with conventional western medicine in COVID-19 (95 % CI of the mean difference was -3.28 to -0.70 days) (8). COVID-19 is a dreadful disease with a huge burden of psychosocial disorders (35). A meta-analysis from India reported several psychological comorbidities ranging from 26% (anxiety and depression) to 40% (poor sleep quality) of study participants (36). The results of the current study were reassuring. Several patients reported early and persistent improvement that was superior in the AYUSH plus arm-reduced anxiety and stress, improved energy and general health and sl...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.06.12.21258345v1 on medRxiv