A double-blind, placebo-controlled, randomized clinical trial to evaluate the efficacy and safety of Virulina® along with standard treatment as per hospital protocol for the treatment of novel coronavirus (COVID-19)
Abstract
Background: There is a high priority for the treatment of mild or moderate COVID-19 in an outpatient setting.
Objective: To test the efficacy, safety and tolerability of Virulina® in mild or moderate COVID-19 patients.
Methods: We carried out a double-blind, placebo-controlled, randomized clinical trial involving adult (18-70yrs) mild or moderate COVID-19 patients, randomized 1:1 on Virulina® (3 gm, maximum 14 days) or placebo respectively along with standard-of-care. The primary endpoint was the time taken for nasopharyngeal swab RT-PCR to test negative. And the average change in the ordinal scale from the baseline scores on the eight-point WHO ordinal scale was assessed.
Results: 30 outpatients were selected between 13 July 2020 to 13 August 2020. 93.33% of Virulina® treated patients were virologically cured compared to 53.33% in the placebo group (p= 0.001). The disappearance rates of major symptoms were significantly high in Virulina® plus standard treatment group compared with standard treatment alone.
Conclusion: Virulina® meets the primary and secondary endpoint criteria and exhibits statistically significant efficacy for mild or moderate COVID-19 patients. It is efficacious, safe, and well-tolerated at the tested dosage of 3gm for a maximum of 14 days.
Keywords: COVID-19; herbal medicine; immunomodulation; clinical trial.
Keywords:
COVID-19, herbal medicine, immunomodulation, clinical trial
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Available at: https://www.who.int/dg/speeches/detail/who-director-general-s-openingremarks-at-the-media-briefing-on-covid-19---11-march-2020. Accessed 19 April 2020.
2. Lai KKR, Wu J, Harris R, McCann A, Collins K, Watkins D, Patel JK. Coronavirus Map: Tracking the Spread of the Outbreak, 2020. https://www.nytimes.com/interactive/2020/world/coronavirusmaps.
3. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Int J Biol Sci. 2020; 15; 16(10):1708-1717. https://doi.org/10.7150/ijbs.45538
4. Liu X, Zhang M, He L, Li Y. Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS). Cochrane Database Syst Rev. 2012; 10(10):CD004882. https://doi.org/10.1002/14651858.CD004882.pub3
5. Luo H, Tang QL, Shang YX, Liang SB, Yang M, Robinson N, Liu JP. Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs. Chin J Integr Med. 2020; 26(4):243-250. https://doi.org/10.1007/s11655-020-3192-6
6. Ang L, Lee HW, Choi JY, Zhang J, Soo Lee M. Herbal medicine and pattern identification for treating COVID-19: a rapid review of guidelines. Integr Med Res. 2020; 9(2):100407. https://doi.org/10.1016/j.imr.2020.100407
7. Chan KW, Wong VT, Tang SCW. COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. Am J Chin Med. 2020; 48(3):737-762. https://doi.org/10.1142/S0192415X20500378
8. Wu YQ, Zou L, Yu X, Sun D, Li SB, Tang L, Yang JR, Chen XY, Wu YG, Fang H. Clinical effects of integrated traditional Chinese and western medicine on COVID-19: A systematic review. Shanghai J Tradit Chin Med. 2020; 1-8. https://doi.org/10.16305/j.1007-1334.2020.06.093 .
9. Qi G, Qi W, Jiang Q, Shen KQ, Zhang X, Zhang L. The Efficacy of Lianhua Qingwen Combined with Western Medicine Scheme on COVID-19 General Type Patients: A Systematic Review. Clin. J. Tradit. Chin Med. 2020; 1-9. Available online: http://kns.cnki.net/kcms/detail/34.1268.r.20200410.0909.002.html.
10. Zhan ZL, Liu J, Yang W, Wang YG, Ruan LG, Huang P, Guo LP, Bian YJ, Chen SP, Chen Y, et al. Exploratory Study on Evaluation Criteria of Chinese Medicine Treatment of New Coronavirus Pneumonia Based on Case Analysis. J. Tradit. Chin. Med. 2020; 1-11. Available online: http://kns.cnki.net/kcms/detail/11.2166.R.20200312.0949.002.html.
11. Jantan I, Haque MA, Ilangkovan M, Arshad L. An Insight Into the Modulatory Effects and Mechanisms of Action of Phyllanthus Species and Their Bioactive Metabolites on the Immune System. Front Pharmacol. 2019; 10:878. https://doi.org/10.3389/fphar.2019.00878
12. Shruthi RR, Venkatesh YP, Muralikrishna G. Structural and functional characterization of a novel immunomodulatory glycoprotein isolated from ajowan (Trachyspermum ammi L.). Glycoconj J. 2017; 34(4):499-514. https://doi.org/10.1007/s10719-017-9771-x
13. Wang HM, Fu L, Cheng CC, Gao R, Lin MY, Su HL, Belinda NE, Nguyen TH, Lin WH, Lee PC, Hsieh LP. Inhibition of LPS-Induced Oxidative Damages and Potential Anti-Inflammatory Effects of Phyllanthus emblica Extract via Down-Regulating NF-κB, COX-2, and iNOS in RAW 264.7 Cells. Antioxidants (Basel). 2019; 8(8):270. https://doi.org/10.3390/antiox8080270
14. Wang P, Yang J, Zhu Z, Zhang X. Marsdenia tenacissima: A Review of Traditional Uses, Phytochemistry and Pharmacology. Am J Chin Med. 2018; 1-32. https://doi.org/10.1142/S0192415X18500751
15. Pang X, Kang LP, Fang XM, Yu HS, Han LF, Zhao Y, Zhang LX, Yu LY, Ma BP. C21 steroid derivatives from the Dai herbal medicine Dai-Bai-Jie, the dried roots of Marsdenia tenacissima, and their screening for anti-HIV activity. J Nat Med. 2018; 72(1):166-180. https://doi.org/10.1007/s11418-017-1126-1
16. Xiang Y, Pei Y, Qu C, Lai Z, Ren Z, Yang K, Xiong S, Zhang Y, Yang C, Wang D, Liu Q. In vitro anti-herpes simplex virus activity of 1,2,4,6-tetra-O-galloyl-β-D-glucose from Phyllanthus emblica L. (Euphorbiaceae). Phytother Res. 2011; 25(7):975-982. https://doi.org/10.1002/ptr.3368
17. Cagno V, Civra A, Kumar R, et al. Ficus religiosa L. bark extracts inhibit human rhinovirus and respiratory syncytial virus infection in vitro. J Ethnopharmacol. 2015; 176:252-257. https://doi.org/10.1016/j.jep.2015.10.042
18. Arbab AH, Parvez MK, Al-Dosari MS, Al-Rehaily AJ. In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus. Exp Ther Med. 2017; 14(1):626-634. https://doi.org/10.3892/etm.2017.4530
19. Fact Sheet for Health Care Providers Emergency Use Authorization of Bamlanivimab and Etesevimab. Eli Lilly, Indianapolis, IN; 2021. Available at: http://pi.lilly.com/eua/bam-and-eteeua-factsheet-hcp.pdf. Accessed 22 August 2023.
20. Fact Sheet for Health Care Providers Emergency Use Authorization of REGEN-COV. Regeneron pharmaceuticals, Inc., Tarrytown, NY; 2021. Available at: https://www.fda.gov/media/145611/download. Accessed 22 August 2023.
21. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021; 384(3):229-237. https://doi.org/10.1056/NEJMoa2029849
22. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021; 384(3):238-251. https://doi.org/10.1056/NEJMoa2035002
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Sewda D, Totade M, Vikram B, Sharma AK. A double-blind, placebo-controlled, randomized clinical trial to evaluate the efficacy and safety of Virulina® along with standard treatment as per hospital protocol for the treatment of novel coronavirus (COVID-19). JDDT [Internet]. 15Sep.2023 [cited 2Oct.2023];13(9):91-7. Available from: https://jddtonline.info/index.php/jddt/article/view/6210
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