Phase III randomized clinical trial of BV ‐4051, an Ayurvedic polyherbal formulation in moderate SARS‐CoV ‐2 infections and its impact on inflammatory biomarkers
Deepa Chitre, Satej Nadkarni, Namdev Jagtap, Rahul Tulle, Amol Gitte, Prashant Rahate, Sunetra Chaskar, Debendranath Dey
Phytotherapy Research, doi:10.1002/ptr.7683
SARS-CoV-2 virus and its variants continue to be a challenge inspite of widespread vaccination and preventive measures. We hypothesized an oral, safe polyherbal formulation with antiinflammatory properties may improve the clinical outcome of this disease. BV-4051, a formulation from four Ayurvedic plants namely Ashwagandha, Boswellia, Ginger and Turmeric was used for the treatment of hospitalized moderate COVID-19 patients along with standard of care (SOC). Patients were randomly assigned to receive BV-4051 or placebo tablets for 14 days, at four sites in India during late 2020 to early 2021. Among 208 randomized subjects, 175 completed the study. In BV-4051 group the mean reduction in duration of illness (p = 0.036), alleviation and severity scores of several symptoms like fever, cough, smell, and taste disorders were statistically significant (p ≤ 0.05). A sub-set analysis of subjects treated with or without Remdesivir as SOC showed mean reduction in duration of illness in BV-4051 (p = 0.030), and severity scores (p ≤ 0.05). Mean difference in Interleukin-6 was statistically significant (p = 0.042) on BV-4051 without Remdesivir. BV-4051 may reduce duration of illness, symptoms severity, Interleukin-6, and prevent the incidence of COVID-19 complications. It may have an adjunctive effect with other SOC. Larger extensive clinical testing may give a better understanding of its effect.
CONFLICT OF INTEREST Deepa Chitre, MD has shares in Bioved Pharmaceuticals, Inc.; Satej Nadkarni, PhD and Debendranath Dey, PhD have stock options in Bioved Pharmaceuticals, Inc.
DATA AVAILABILITY STATEMENT All of the individual participant data collected during the trial, Study Protocol, Statistical Analytical Plan, Informed Consent Form and Clinical Study Report shall be available immediately after publication, for a period of 5 years. Researchers who provide an interest and methodologically sound proposal should contact dchitre@bioved.com with a copy to snadkarni@bioved.com. To gain access, researchers will need to sign a data access agreement. Placeholder Text
ORCID
SUPPORTING INFORMATION Additional supporting information can be found online in the Supporting Information section at the end of this article. How to cite this article: Chitre, D., Nadkarni, S., Jagtap, N., Tulle, R., Gitte, A., Rahate, P., Chaskar, S., & Dey, D. (2022) . Phase III randomized clinical trial of BV-4051, an Ayurvedic polyherbal formulation in moderate SARS-CoV-2 infections and its impact on inflammatory biomarkers. Phytotherapy Research, 1-10. https://doi.org/10.1002/ptr.7683
References
Abdalhamid, Donahue, Kamal-Ahmed, Strand, Mitchell et al., Identification of SARS-CoV-2 variants of concern in vaccine-breakthrough infections, Journal of Infection in Developing Countries,
doi:10.3855/jidc.15458Accorsi, Britton, Fleming-Dutra, Smith, Shang et al., Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 omicron and delta variants, Journal of the American Medical Association,
doi:10.1001/jama.2022.0470Ahmad, Zahiruddin, Parveen, Basist, Parveen et al., Indian medicinal plants and formulations and their potential against COVID-19-preclinical and clinical research, Frontiers in Pharmacology,
doi:10.3389/fphar.2020.578970Batista, Foti, Anti-SARS-CoV-2 and anti-cytokine storm neutralizing antibody therapies against COVID-19: update, challenges, and perspectives, International Immunopharmacology,
doi:10.1016/j.intimp.2021.108036Bernal, Gomes Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients, The New England Journal of Medicine,
doi:10.1056/NEJMoa2116044Birhane, Bressler, Chang, Clark, Dorough et al., COVID-19 Vaccine breakthrough infections reported to CDC -United States, Morbidity and Mortality Weekly Report,
doi:10.15585/mmwr.mm7021e3Boozari, Hosseinzadeh, Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies, Phytotherapy Research,
doi:10.1002/ptr.6873Cairns, Dulko, Griffiths, Golan, Cohen et al., Efficacy of niclosamide vs placebo in SARS-CoV-2 respiratory viral clearance, viral shedding, and duration of symptoms among patients with mild to moderate COVID-19: A Phase 2 randomized clinical trial, JAMA Network Open,
doi:10.1001/jamanetworkopen.2021.44942Chang, Wang, Yeh, Shieh, Chiang, Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines, Journal of Ethnopharmacology,
doi:10.1016/j.jep.2012.10.043Chaskar, None
Chen, Lin, Zhao, Sun, Tian et al., A low-producing haplotype of interleukin-6 disrupting CTCF binding is protective against Severe COVID-19, Clinical Microbiology,
doi:10.1128/mBio.01372-21Chitre, Dey, Method for extraction of fractions containing pharmacologically active ingredients with less cytotoxicity from one or more plants, US Patent issued
Chopra, Lavin, Patwardhan, Chitre, Randomized double-blind placebo-controlled trial of efficacy and safety in rheumatoid arthritis, Journal of Rheumatology
Chopra, Lavin, Patwardhan, Chitre, Randomized double-blind placebo-controlled trial of efficacy and safety, in particular VAS and WOMAC, in osteoarthritis of Knee, Journal of Clinical Rheumatology
Chopra, Saluja, Kianifard, Chitre, Venugopalan, Long term effectiveness of RA-1 as a monotherapy and in combination with disease modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis, Journal of Ayurveda and Integrative Medicine,
doi:10.4103/0975-9476.72620Dey, Chaskar, Athavale, Chitre, Acute and chronic toxicity, cytochrome p450 enzyme inhibition, and HERG channel blockade studies with a polyherbal, ayurvedic formulation for inflammation,
doi:10.1155/2015/971982Dey, Chaskar, Athavale, Chitre, Inhibition of LPSinduced TNF-α and NO production in mouse macrophage and inflammatory response in rat animal models by a novel ayurvedic formulation, BV-9238, Phytotherapy Research,
doi:10.1002/ptr.5151Dey, None
Emadi, Chua, Talwani, Bentzen, Baddley, Safety and efficacy of imatinib for hospitalized adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial, Trials,
doi:10.1186/s13063-020-04819-9Fan, Gu, Alemi, Chinese herbal medicine for COVID-19 current evidence with systematic review and meta-analysis, Journal of Integrative Medicine,
doi:10.1016/j.joim.2020.07.008Feldman, Maini, Woody, Holgate, Winter et al., Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed, Lancet,
doi:10.1016/S0140-6736(20)30858-8Gao, Xiuying, Jiao, Wang, Reinfection and breakthrough Infection of SARS-CoV-2: An emerging challenge that is threatening our world, Infectious Diseases and Immunity,
doi:10.1097/ID9.0000000000000027Gomaa, Mohamed, Abd-Ellatief, Gomaa, Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly, Inflammopharmacology,
doi:10.1007/s10787-021-00841-8Gottlieb, Vaca, Paredes, Mera, Webb et al., Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients, The New England Journal of Medicine,
doi:10.1056/nejmoa2116846Han, Ma, Li, Liu, Zhao et al., Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors, Emerging Microbes & Infections,
doi:10.1080/22221751.2020.1770129Herold, Jurinovic, Arnreich, Lipworth, Hellmuth et al., Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19, The Journal of Allergy and Clinical Immunology,
doi:10.1016/j.jaci.2020.05.008Ichsyani, Ridhanya, Risanti, Desti, Ceria et al., Antiviral effects of Curcuma longa L. against dengue virus in vitro and in vivo, IOP Conference Series: Earth and Environmental Science,
doi:10.1088/1755-1315/101/1/012005Izadi, Brenner, Mahil, Dand, Yiu et al., Association between tumor necrosis factor inhibitors and the risk of hospitalization or death among patients with immune-mediated inflammatory disease and COVID-19, JAMA Network Open,
doi:10.1001/jamanetworkopen.2021.29639Kumar, Rai, Khan, Amit, Haque et al., Role of herbal medicines in the management of patients with Covid-19: A systematic review and meta-analysis of randomized controlled trials, Journal of Traditional and Complementary Medicine,
doi:10.1016/j.jtcme.2022.01.002Magro, SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the 'culprit lesion' of ARDS onset? What is there besides Tocilizumab?, Cytokine X,
doi:10.1016/j.cytox.2020.100029Patil, Hupparage, Malgi, Deshpande, Patil et al., Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera, Chinese Herbal Medicines,
doi:10.1016/j.chmed.2021.06.002Rahate, None
Rasool, Khan, Ali, Anjum, Ahmed et al., Anti-Avian influenza virus H9N2 activity of aqueous extracts of Zingiber officinalis (Ginger) and Allium sativum (Garlic) in chick embryos, Pakistan Journal of Pharmaceutical Sciences
Saggam, Limgaokar, Borse, Dixit, Tillu et al., Withania somnifera (L.) Dunal: Opportunity for Clinical repurposing in COVID-19 Management, Frontiers in Pharmacology,
doi:10.3389/fphar.2021.623795Salama, Han, Yau, Reiss, Kramer et al., Tocilizumab in patients hospitalized with Covid-19 pneumonia, The New England Journal of Medicine,
doi:10.1056/NEJMoa2030340Sarkar, Chakrabarti, Dutta, Covid-19 infection in India: A comparative analysis of the second wave with the first wave, Pathogens,
doi:10.3390/pathogens10091222Sheikh, Pal, Javed, Shekhar, COVID-19 vaccination in developing nations: Challenges and opportunities for innovation, Infectious Disease Reports,
doi:10.3390/idr13020041Sornpet, Potha, Tragoolpua, Pringproa, Antiviral activity of five Asian medicinal plant crude extracts against highly pathogenic H5N1 avian influenza virus, Asian Pacific Journal of Tropical Medicine,
doi:10.1016/j.aptm.2017.08.010Srivastava, Rengaraju, Srivastava, Narayanan, Gupta et al., Efficacy of two siddha polyherbal decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with standard allopathy treatment in the management of mild to moderate symptomatic COVID-19 patients-a double-blind, placebo-controlled, clinical trial, Trials,
doi:10.1186/s13063-021-05478-0Tiwari, Gupta, Pathak, A double-blind, randomized, placebo-controlled trail on the effect of Ashwagandha (Withania somnifera dunal) root extract in improving cardiorespiratory endurance and recovery in healthy athletic adults, Journal of Ethnopharmacology,
doi:10.1016/j.jep.2021.113929Treanor, Hayden, Vrooman, Barbarash, Bettis et al., Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial, Journal of the American Medical Association,
doi:10.1001/jama.283.8.1016Trunfio, Verga, Ghisetti, Burdino, Emanuele et al., Clinical phenotype and contagiousness of early breakthrough SARS-CoV-2 infections after BNT162b2 COVID-19 mRNA vaccine: A Parallel Cohort Study in Healthcare Workers, Vaccine,
doi:10.3390/vaccines9121377Whitley, Molnupiravir -A Step toward orally bioavailable therapies for Covid-19, The New England Journal of Medicine,
doi:10.1056/NEJMe2117814Xiong, Wang, Su, Cho, Xing, Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta-analysis, Pharmacological Research,
doi:10.1016/j.phrs.2020.105056Zhao, Li, Zhong, Mechanism of action of small-molecule agents in ongoing clinical trials for SARS-CoV-2: A review, Frontiers in Pharmacology,
doi:10.3389/fphar.2022.840639DOI record:
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