Jinhua Qinggan granules for non-hospitalized COVID-19 patients: A double-blind, placebo-controlled, and randomized controlled trial

  1. Muhammad Raza Shah
  2. Samreen Fatima
  3. Sehrosh Naz Khan
  4. Shafi Ullah
  5. Gulshan Himani
  6. Kelvin Wan
  7. Timothy Lin
  8. Johnson Y. N. Lau
  9. Qingquan Liu
  10. Dennis S. C. Lam

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Abstract

Key findings from the World Health Organization Expert Meeting on Evaluation of Traditional Chinese Medicine (TCM) in treating coronavirus disease 2019 (COVID-19) reported that TCMs are beneficial, particularly for mild-to-moderate cases. The efficacy of Jinhua Qinggan granules (JHQG) in COVID-19 patients with mild symptoms has yet to be clearly defined.

Methods

We conducted a phase 2/3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with JHQG in mild, non-hospitalized, laboratory-confirmed COVID-19 patients. Participants were randomly assigned to receive 5 g/sacket of JHQG or placebo granules orally thrice daily for 10 days. The primary outcomes were the improvement in clinical symptoms and a proportion tested negative on viral polymerase chain reaction (PCR) after treatment. Secondary outcomes were the time to recover from clinical symptoms and changes in white blood cells (WBC) and acute phase reactants (C-reactive protein (CRP) and ferritin) on the 10th day after treatment initiation.

Results

A total of 300 patients were randomly assigned to receive JHQG (150 patients) and placebo (150 patients). Baseline characteristics were similar in the two groups. In the modified intention-to-treat analysis, JHQG showed greater clinical efficacy (82.67%) on the 10th day of the trial compared with the placebo group (10.74%; rate difference: 71.93%; 95% CI 64.09–79.76). The proportion of patients with a negative PCR after treatment was comparable (rate difference: −4.67%; 95% CI −15.76 to 6.42). In contrast, all changes in WBC, ferritin, and CRP levels showed a statistically significant decline in JHQG ( P ≤ 0.044) after treatment, but not the latter in placebo ( P = 0.077). The median time to recovery of COVID-19-related symptoms including cough, sputum, sore throat, dyspnea, headache, nasal obstruction, fatigue, and myalgia was shorter in the JHQG group compared to the placebo group ( P < 0.001 for all). Three patients experienced mild-to-moderate adverse events (AEs) duringthe treatment period in the JHQG group. Findings were similar between the modified intention-to-treat and the per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen.

Conclusion

Based on the time to recover from the COVID-19-related symptoms and AEs, it is concluded that JHQG is a safe and effective TCM for symptomatic relief of patients with mild COVID-19. A symptomatic improvement in the JHQG group patients was observed and JHQG use would have important public health implications in such patients.

Clinical Trial Registration

The Trial was prospectively registered on www.clinicaltrials.gov with registration number: NCT04723524.

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  1. Version published to 10.3389/fmed.2022.928468
  2. ScreenIT

    SciScore for 10.1101/2022.05.16.22275074: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the Institutional Ethics Committee of International Center for chemical and biological Sciences (ICCBS) and institutional review board of the Indus Hospital (Sector 39, Karachi, Sindh, Pakistan).
    Consent: All study participants provided written informed consent before enrolling in the clinical trial.
    Sex as a biological variablePatients were excluded if they had any of the following: (1) previous confirmed SARS-CoV-2 infection; (2) moderate or critical COVID-19 infection with (a) respiratory failure and requiring mechanical ventilation, (b) shock, or (c) other organ failure requiring intensive care unit (ICU) support; (3) severe primary health conditions associated with cardiovascular, cerebrovascular, pulmonary, hepatic, renal, endocrine and hematological diseases, hematopoietic system (above grade II of cardiac function; ALT & AST are 1.5 times higher than the normal value; Creatinine above the upper limit of normal value) and mental illness or serious diseases affecting their survival, such as cancer or AIDS; (4) administered other antiviral, antibiotics, cough relieving and antihistamine medications within 3 days prior to the visit (including β2 receptor agonists, anticholinergic agents, theophylline, glucocorticoids, cough expectorant and other TCM); (5) history of drug or food allergy; (6) pregnancy, lactating, or fertile women who were planning to conceive in 3 months; and (7) participated in another clinical study in the past 1 month.
    RandomizationThis phase 2-3, double-blind, randomized, placebo-controlled clinical trial evaluated the efficacy and safety associated with the use of JHQG among nonhospitalized COVID-19 adult Pakistani patients with mild symptoms.
    BlindingPatients and investigators in this trial were blinded to the treatment allocation until the completion of the study.
    Power Analysis2.2 Sample Size Calculation: The sample size was based on detecting a 20% difference in recovery from COVID-19 related symptoms.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis was performed using SPSS (version 23.0; IBM, NY, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Various limitations of this trial should be noted. The basic reason for dropout was that the subjects were unable or unwilling to continue the clinical trial and voluntarily requested to withdraw The study included only COVID-19 patients of Pakistani race, and may limit the geographic generalizability of the findings. This study also excluded patients with severe underlying medical conditions, who are at particularly heightened risk of COVID-19 disease progression. Future studies of JHQG in COVID-19 shall focus on evaluating the clinical efficacy and safety of this TCM in such group of patients. In conclusion, our data show that JHQG is a safe and effective treatment for COVID-19 patients with mild symptoms.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04723524CompletedJinhua Qinggan Granules in the Treatment of COVID-19

    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.

  3. Version published to 10.1101/2022.05.16.22275074v2 on medRxiv
  4. Version published to 10.1101/2022.05.16.22275074v1 on medRxiv