Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial

{ 'indexed': { 'date-parts': [[2023, 11, 29]], 'date-time': '2023-11-29T01:03:53Z', 'timestamp': 1701219833434}, 'reference-count': 23, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T00:00:00Z', 'timestamp': 1701129600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T00:00:00Z', 'timestamp': 1701129600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'name': 'Innovation Team and Talents Cultivation Program of National Administration of ' 'Traditional Chinese Medicine', 'award': ['No: ZYYCXTD-D-202206']}, {'name': 'the Science and Technology Program of Hebei', 'award': ['225A2503D']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective ' 'for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). ' 'However, the lack of blinding and limited sample sizes decreased the level of clinical ' 'evidence.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Objectives</jats:title>\n' ' <jats:p>To evaluate the efficacy and safety of LHQW capsule in adults with ' 'mild-to-moderate COVID-19.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>We conducted a double-blind randomized controlled trial in adults ' 'with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). ' 'Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for ' '14 days. The primary endpoint was the median time to sustained clinical improvement or ' 'resolution of nine major symptoms.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>The full-analysis set consisted of 410 patients in LHQW capsules and ' '405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis ' 'set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW ' 'capsules shortened the median time to sustained clinical improvement or resolution of stuffy ' 'or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), ' 'feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and ' 'myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of ' 'shortness of breath, headache, and chills or shivering did not differ significantly between ' 'the two groups. Safety was comparable between the two groups. No serious adverse events were ' 'reported.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Interpretation</jats:title>\n' ' <jats:p>LHQW capsules promote recovery of mild-to-moderate COVID-19 via ' 'accelerating symptom resolution and were well tolerated.</jats:p>\n' ' <jats:p><jats:italic>Trial registration</jats:italic><jats:ext-link ' 'xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" ' 'xlink:href="https://clinicaltrials.gov/ct2/show/ChiCTR2200056727">ChiCTR2200056727</jats:ext-link>.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s12985-023-02144-6', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T16:02:58Z', 'timestamp': 1701187378000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an ' 'international, multicenter, double-blind, randomized controlled trial', 'prefix': '10.1186', 'volume': '20', 'clinical-trial-number': [{'clinical-trial-number': 'chictr2200056727', 'registry': '10.18810/chictr'}], 'author': [ {'given': 'Jin-ping', 'family': 'Zheng', 'sequence': 'first', 'affiliation': []}, {'given': 'Yun', 'family': 'Ling', 'sequence': 'additional', 'affiliation': []}, {'given': 'Liang-shuang', 'family': 'Jiang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Piroon', 'family': 'Mootsikapun', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hong-zhou', 'family': 'Lu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Methee', 'family': 'Chayakulkeeree', 'sequence': 'additional', 'affiliation': []}, {'given': 'Li-xiu', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pureepat', 'family': 'Arttawejkul', 'sequence': 'additional', 'affiliation': []}, {'given': 'Feng-yu', 'family': 'Hu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Thi Ngoc Lan', 'family': 'Truong', 'sequence': 'additional', 'affiliation': []}, {'given': 'Roxan A.', 'family': 'Perez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Xing', 'family': 'Gu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hui-min', 'family': 'Sun', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jian-jie', 'family': 'Jiang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ren-jie', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Zhen', 'family': 'Ding', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yang-qing', 'family': 'Zhan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Zi-feng', 'family': 'Yang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wei-jie', 'family': 'Guan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nan-shan', 'family': 'Zhong', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 11, 28]]}, 'reference': [ { 'key': '2144_CR1', 'unstructured': 'World Health Organization Coronavirus (COVID-19) Dashboard ' '[https://covid19.who.int/]'}, { 'issue': '10332', 'key': '2144_CR2', 'doi-asserted-by': 'publisher', 'first-page': '1303', 'DOI': '10.1016/S0140-6736(22)00462-7', 'volume': '399', 'author': 'T Nyberg', 'year': '2022', 'unstructured': 'Nyberg T, Ferguson NM, Nash SG, Webster HH, Flaxman S, Andrews N, ' 'Hinsley W, Bernal JL, Kall M, Bhatt S, et al. Comparative analysis of ' 'the risks of hospitalisation and death associated with SARS-CoV-2 ' 'omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort ' 'study. Lancet. 2022;399(10332):1303–12.', 'journal-title': 'Lancet'}, { 'key': '2144_CR3', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lanwpc.2022.100592', 'volume': '29', 'author': 'Z Chen', 'year': '2022', 'unstructured': 'Chen Z, Deng X, Fang L, Sun K, Wu Y, Che T, Zou J, Cai J, Liu H, Wang Y, ' 'et al. Epidemiological characteristics and transmission dynamics of the ' 'outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a ' 'descriptive study. Lancet Reg Health West Pac. 2022;29: 100592.', 'journal-title': 'Lancet Reg Health West Pac'}, { 'issue': '9', 'key': '2144_CR4', 'doi-asserted-by': 'publisher', 'first-page': '790', 'DOI': '10.1056/NEJMoa2204919', 'volume': '387', 'author': 'R Arbel', 'year': '2022', 'unstructured': 'Arbel R, Wolff Sagy Y, Hoshen M, Battat E, Lavie G, Sergienko R, Friger ' 'M, Waxman JG, Dagan N, Balicer R, et al. Nirmatrelvir use and severe ' 'Covid-19 outcomes during the omicron surge. N Engl J Med. ' '2022;387(9):790–8.', 'journal-title': 'N Engl J Med'}, { 'issue': '6', 'key': '2144_CR5', 'doi-asserted-by': 'publisher', 'first-page': '509', 'DOI': '10.1056/NEJMoa2116044', 'volume': '386', 'author': 'BA Jayk', 'year': '2022', 'unstructured': 'Jayk BA, da Gomes SMM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos RV, ' 'Martín-Quirós A, Caraco Y, Williams-Diaz A, Brown ML, et al. ' 'Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. ' 'N Engl J Med. 2022;386(6):509–20.', 'journal-title': 'N Engl J Med'}, { 'key': '2144_CR6', 'first-page': '21', 'volume': '5', 'author': 'Z Cao', 'year': '2022', 'unstructured': 'Cao Z, Gao W, Bao H, Feng H, Mei S, Chen P, Gao Y, Cui Z, Zhang Q, Meng ' 'X, et al. VV116 versus nirmatrelvir-ritonavir for oral treatment of ' 'Covid-19. N Engl J Med. 2022;5:21.', 'journal-title': 'N Engl J Med'}, { 'issue': '23', 'key': '2144_CR7', 'doi-asserted-by': 'publisher', 'first-page': '2188', 'DOI': '10.1056/NEJMoa2116620', 'volume': '386', 'author': 'MJ Levin', 'year': '2022', 'unstructured': 'Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, Yuan ' 'Y, Seegobin S, Ellery A, Levinson DJ, et al. Intramuscular AZD7442 ' '(Tixagevimab-Cilgavimab) for prevention of Covid-19. N Engl J Med. ' '2022;386(23):2188–200.', 'journal-title': 'N Engl J Med'}, { 'issue': '21', 'key': '2144_CR8', 'doi-asserted-by': 'publisher', 'first-page': '1941', 'DOI': '10.1056/NEJMoa2107934', 'volume': '385', 'author': 'A Gupta', 'year': '2021', 'unstructured': 'Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, ' 'Sarkis E, Solis J, Zheng H, Scott N, et al. Early treatment for Covid-19 ' 'with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med. ' '2021;385(21):1941–50.', 'journal-title': 'N Engl J Med'}, { 'issue': '16', 'key': '2144_CR9', 'doi-asserted-by': 'publisher', 'first-page': '1491', 'DOI': '10.1056/NEJMoa2100433', 'volume': '384', 'author': 'AC Gordon', 'year': '2021', 'unstructured': 'Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, Arabi YM, Annane ' 'D, Beane A, van Bentum-Puijk W, Berry LR, et al. Interleukin-6 receptor ' 'antagonists in critically Ill patients with Covid-19. N Engl J Med. ' '2021;384(16):1491–502.', 'journal-title': 'N Engl J Med'}, { 'issue': '5', 'key': '2144_CR10', 'doi-asserted-by': 'publisher', 'first-page': '406', 'DOI': '10.1056/NEJMoa2101643', 'volume': '385', 'author': 'PO Guimarães', 'year': '2021', 'unstructured': 'Guimarães PO, Quirk D, Furtado RH, Maia LN, Saraiva JF, Antunes MO, ' 'Kalil Filho R, Junior VM, Soeiro AM, Tognon AP, et al. Tofacitinib in ' 'patients hospitalized with Covid-19 pneumonia. N Engl J Med. ' '2021;385(5):406–15.', 'journal-title': 'N Engl J Med'}, { 'issue': '9', 'key': '2144_CR11', 'doi-asserted-by': 'publisher', 'first-page': '795', 'DOI': '10.1056/NEJMoa2031994', 'volume': '384', 'author': 'AC Kalil', 'year': '2021', 'unstructured': 'Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, ' 'Marconi VC, Ruiz-Palacios GM, Hsieh L, Kline S, et al. Baricitinib plus ' 'remdesivir for hospitalized adults with Covid-19. N Engl J Med. ' '2021;384(9):795–807.', 'journal-title': 'N Engl J Med'}, { 'key': '2144_CR12', 'unstructured': 'Ministry of Health C: the Protocol of the Diagnosis and Treatment of ' 'Coronavirus Disease 2019. In: 2023'}, { 'key': '2144_CR13', 'doi-asserted-by': 'publisher', 'first-page': '104761', 'DOI': '10.1016/j.phrs.2020.104761', 'volume': '156', 'author': 'L Runfeng', 'year': '2020', 'unstructured': 'Runfeng L, Yunlong H, Jicheng H, Weiqi P, Qinhai M, Yongxia S, Chufang ' 'L, Jin Z, Zhenhua J, Haiming J, et al. Lianhuaqingwen exerts anti-viral ' 'and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). ' 'Pharmacol Res. 2020;156:104761.', 'journal-title': 'Pharmacol Res'}, { 'issue': '08', 'key': '2144_CR14', 'first-page': '655', 'volume': '61', 'author': 'LWW Ruibing', 'year': '2020', 'unstructured': 'Ruibing LWW, Xin L. Clinical observation on 63 cases of suspected cases ' 'of new coronavirus pneumonia treated by Chinese medicine Lianhua ' 'Qingwen. J Tradit Chin Med. 2020;61(08):655–9.', 'journal-title': 'J Tradit Chin Med'}, { 'key': '2144_CR15', 'doi-asserted-by': 'publisher', 'first-page': '153242', 'DOI': '10.1016/j.phymed.2020.153242', 'volume': '85', 'author': 'K Hu', 'year': '2021', 'unstructured': 'Hu K, Guan WJ, Bi Y, Zhang W, Li L, Zhang B, Liu Q, Song Y, Li X, Duan ' 'Z, et al. Efficacy and safety of Lianhuaqingwen capsules, a repurposed ' 'Chinese herb, in patients with coronavirus disease 2019: A multicenter, ' 'prospective, randomized controlled trial. Phytomedicine. 2021;85:153242.', 'journal-title': 'Phytomedicine'}, { 'issue': '5', 'key': '2144_CR16', 'doi-asserted-by': 'publisher', 'first-page': '2859', 'DOI': '10.21037/jtd-23-281', 'volume': '15', 'author': 'YQCR Zhan', 'year': '2023', 'unstructured': 'Zhan YQCR, Zheng QS, et al. Efficacy and safety of LianhuaQingwen ' 'capsules combined with standard of care in the treatment of adult ' 'patients with mild to moderate COVID-19 (FLOSAN): protocol for a ' 'randomized, double-blind, international multicenter clinical trial. J ' 'Thorac Dis. 2023;15(5):2859–72.', 'journal-title': 'J Thorac Dis'}, { 'key': '2144_CR17', 'unstructured': 'Organization WH: World Health Organization the 5th interim guidelines ' 'for COVID-19. In.: World Health Organization; 2020.'}, { 'issue': '7902', 'key': '2144_CR18', 'doi-asserted-by': 'publisher', 'first-page': '715', 'DOI': '10.1038/s41586-022-04479-6', 'volume': '603', 'author': 'KPY Hui', 'year': '2022', 'unstructured': 'Hui KPY, Ho JCW, Cheung MC, Ng KC, Ching RHH, Lai KL, Kam TT, Gu H, Sit ' 'KY, Hsin MKY, et al. SARS-CoV-2 Omicron variant replication in human ' 'bronchus and lung ex vivo. Nature. 2022;603(7902):715–20.', 'journal-title': 'Nature'}, { 'issue': '7', 'key': '2144_CR19', 'doi-asserted-by': 'publisher', 'first-page': '650', 'DOI': '10.1007/s11655-022-3578-8', 'volume': '28', 'author': 'XH Sun', 'year': '2022', 'unstructured': 'Sun XH, Zhang S, Yang Z, Chen ZL, Yue SJ, Zhang S, Tang YP. Efficacy and ' 'safety of Lianhua Qingwen for patients with COVID-19: a systematic ' 'review and meta-analysis. Chin J Integr Med. 2022;28(7):650–60.', 'journal-title': 'Chin J Integr Med'}, { 'key': '2144_CR20', 'doi-asserted-by': 'publisher', 'first-page': '102754', 'DOI': '10.1016/j.ctim.2021.102754', 'volume': '60', 'author': 'J Zhuang', 'year': '2021', 'unstructured': 'Zhuang J, Dai X, Wu Q, Cai H, Fu X, Zhang W, Chen B. A meta-analysis for ' 'Lianhua Qingwen on the treatment of Coronavirus disease 2019 (COVID-19). ' 'Complement Ther Med. 2021;60:102754.', 'journal-title': 'Complement Ther Med'}, { 'issue': '21', 'key': '2144_CR21', 'doi-asserted-by': 'publisher', 'first-page': 'e26059', 'DOI': '10.1097/MD.0000000000026059', 'volume': '100', 'author': 'Z Fan', 'year': '2021', 'unstructured': 'Fan Z, Guo G, Che X, Yang Y, Liu Y, Li L, Chang X, Han L, Cai X, Tang H. ' 'Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus ' 'disease 2019: a meta-analysis of randomized controlled trials. Medicine ' '(Baltimore). 2021;100(21):e26059.', 'journal-title': 'Medicine (Baltimore)'}, { 'issue': '1', 'key': '2144_CR22', 'doi-asserted-by': 'publisher', 'first-page': '100644', 'DOI': '10.1016/j.imr.2020.100644', 'volume': '10', 'author': 'M Liu', 'year': '2021', 'unstructured': 'Liu M, Gao Y, Yuan Y, Yang K, Shi S, Tian J, Zhang J. Efficacy and ' 'safety of herbal medicine (Lianhuaqingwen) for treating COVID-19: a ' 'systematic review and meta-analysis. Integr Med Res. 2021;10(1):100644.', 'journal-title': 'Integr Med Res'}, { 'key': '2144_CR23', 'doi-asserted-by': 'publisher', 'first-page': '7962630', 'DOI': '10.1155/2021/7962630', 'volume': '2021', 'author': 'X Gong', 'year': '2021', 'unstructured': 'Gong X, Yuan B, Yuan Y, Li F. Efficacy and safety of Lianhuaqingwen ' 'capsules for the prevention of coronavirus disease 2019: a prospective ' 'open-label controlled trial. Evid Based Complement Alternat Med. ' '2021;2021:7962630.', 'journal-title': 'Evid Based Complement Alternat Med'}], 'container-title': 'Virology Journal', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12985-023-02144-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12985-023-02144-6/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12985-023-02144-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 28]], 'date-time': '2023-11-28T16:08:35Z', 'timestamp': 1701187715000}, 'score': 1, 'resource': {'primary': {'URL': 'https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02144-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 28]]}, 'references-count': 23, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2023, 12]]}}, 'alternative-id': ['2144'], 'URL': 'http://dx.doi.org/10.1186/s12985-023-02144-6', 'relation': {}, 'ISSN': ['1743-422X'], 'subject': ['Infectious Diseases', 'Virology'], 'container-title-short': 'Virol J', 'published': {'date-parts': [[2023, 11, 28]]}, 'assertion': [ { 'value': '31 May 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '26 July 2023', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '28 November 2023', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Ethics approval has been obtained the ethics committee of each participating ' 'site, based on <i>Good Clinical Practice</i>. All patients signed written ' 'informed consent.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'None.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '277'}