{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:12:27Z","timestamp":1753891947982,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To evaluate the efficacy and safety of Hengli<jats:sup>\u00ae<\/jats:sup> Chinese botulinum toxin type A (BTX-A; 100 U) in Chinese patients with overactive bladder.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This study was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese patients who were inadequately managed with anticholinergic medications. Eligible patients were randomized 2:1 to receive intradetrusor injections of Hengli<jats:sup>\u00ae<\/jats:sup> BTX-A (<jats:italic>n<\/jats:italic> = 144) or placebo (<jats:italic>n<\/jats:italic> = 72). The primary endpoint was the change in the number of daily micturition episodes at week 6 from baseline. The secondary efficacy endpoints included the average frequency of urgency and urinary incontinence (UI) episodes per day, urgency score, average micturition volume per day, OABSS, and QoL score.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In the Hengli<jats:sup>\u00ae<\/jats:sup> BTX-A group, there was a significantly greater reduction in the average number of micturition episodes per 24\u00a0h compared with the placebo group (3.28 vs. 1.43; <jats:italic>p<\/jats:italic> = 0.003). Moreover, there was a significantly greater improvement in the daily number of urgency episodes, micturition volume and OABSS score. An increased post-void residual urine volume, dysuria, and urinary tract infection represented adverse events (AEs) in the Hengli<jats:sup>\u00ae<\/jats:sup> BTX-A group. Most AEs were mild or moderate in severity. One patient in the BTX-A group initiated clean intermittent catheterization (CIC) during treatment.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Hengli<jats:sup>\u00ae<\/jats:sup> BTX-A treatment was well-tolerated and resulted in significant improvements in OAB symptoms among Chinese patients inadequately managed by anticholinergics.<\/jats:p><jats:p><jats:bold>Clinical Trial Registration:<\/jats:bold><jats:ext-link>http:\/\/www.chinadrugtrials.org.cn\/clinicaltrials.prosearch.dhtml<\/jats:ext-link>, Identifier: CTR20131190.<\/jats:p>","DOI":"10.3389\/fphar.2022.840695","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T07:08:23Z","timestamp":1645168103000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hengli\u00ae Chinese Botulinum Toxin Type A for Treatment of Patients With Overactive Bladder: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Limin","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinggang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiling","family":"Cong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiliang","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujie","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guowei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peijun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zujun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghao","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanzhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxiang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianlong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keji","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinkai","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/nau.10052","article-title":"The Standardisation of Terminology of Lower Urinary Tract Function: Report from the Standardisation Sub-committee of the International Continence Society","volume":"21","author":"Abrams","year":"2002","journal-title":"Neurourol Urodyn"},{"key":"B2","first-page":"S580","article-title":"Overactive Bladder Significantly Affects Quality of Life","volume":"6","author":"Abrams","year":"2000","journal-title":"Am. J. Manag. Care"},{"key":"B3","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3109\/01443615.2011.649317","article-title":"An Overview of Treatment of Overactive Bladder Syndrome in Women","volume":"32","author":"Allahdin","year":"2012","journal-title":"J. Obstet. Gynaecol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.eururo.2005.12.010","article-title":"Proposed Mechanism for the Efficacy of Injected Botulinum Toxin in the Treatment of Human Detrusor Overactivity","volume":"49","author":"Apostolidis","year":"2006","journal-title":"Eur. Urol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1097\/01.ju.0000169481.42259.54","article-title":"Decreased Sensory Receptors P2X3 and TRPV1 in Suburothelial Nerve Fibers Following Intradetrusor Injections of Botulinum Toxin for Human Detrusor Overactivity","volume":"174","author":"Apostolidis","year":"2005","journal-title":"J. Urol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1111\/j.1464-410X.2009.09036.x","article-title":"Patient-reported Reasons for Discontinuing Overactive Bladder Medication","volume":"105","author":"Benner","year":"2010","journal-title":"BJU Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.eururo.2008.11.026","article-title":"Tolterodine Treatment Improves Storage Symptoms Suggestive of Overactive Bladder in Men Treated with Alpha-Blockers","volume":"56","author":"Chapple","year":"2009","journal-title":"Eur. Urol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.eururo.2013.04.001","article-title":"OnabotulinumtoxinA 100 U Significantly Improves All Idiopathic Overactive Bladder Symptoms and Quality of Life in Patients with Overactive Bladder and Urinary Incontinence: a Randomised, Double-Blind, Placebo-Controlled Trial","volume":"64","author":"Chapple","year":"2013","journal-title":"Eur. Urol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/luts.12193","article-title":"Prevalence of Overactive Bladder in China, Taiwan and South Korea: Results from a Cross-Sectional, Population-Based Study","volume":"11","author":"Chuang","year":"2019","journal-title":"Low Urin Tract Symptoms"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1111\/bju.12266","article-title":"OnabotulinumtoxinA Significantly Attenuates Bladder Afferent Nerve Firing and Inhibits ATP Release from the Urothelium","volume":"112","author":"Collins","year":"2013","journal-title":"BJU Int."},{"key":"B11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/nau.22445","article-title":"Targets for Botulinum Toxin in the Lower Urinary Tract","volume":"33","author":"Cruz","year":"2014","journal-title":"Neurourol Urodyn"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e147","DOI":"10.1016\/j.eururo.2020.12.03210.1016\/j.eururo.2021.02.033","article-title":"Reply to Satoshi Funada, Takashi Yoshioka, and Yan Luo's Letter to the Editor re: Cosimo De Nunzio, Benjamin Brucker, Thomas Bschleipfer, et al. Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men. Eur Urol 2021;79:492-504","volume":"79","author":"De Nunzio","year":"2021","journal-title":"Eur. Urol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.toxicon.2019.12.005","article-title":"Therapeutically Relevant Features of Botulinum Toxin Drugs","volume":"175","author":"Dressler","year":"2020","journal-title":"Toxicon"},{"key":"B14","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.urology.2006.02.042","article-title":"Symptom Assessment Tool for Overactive Bladder Syndrome-Ooveractive Bladder Symptom Score","volume":"68","author":"Homma","year":"2006","journal-title":"Urology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1111\/j.1464-410X.2010.09993.x","article-title":"Worldwide Prevalence Estimates of Lower Urinary Tract Symptoms, Overactive Bladder, Urinary Incontinence and Bladder Outlet Obstruction","volume":"108","author":"Irwin","year":"2011","journal-title":"BJU Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1111\/j.1464-410X.2005.05889.x","article-title":"Impact of Overactive Bladder Symptoms on Employment, Social Interactions and Emotional Well-Being in Six European Countries","volume":"97","author":"Irwin","year":"2006","journal-title":"BJU Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrurol.2015.193","article-title":"Current and Potential Urological Applications of Botulinum Toxin A","volume":"12","author":"Jiang","year":"2015","journal-title":"Nat. Rev. Urol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.neuint.2004.06.001","article-title":"Botulinum Toxin A Inhibits ATP Release from Bladder Urothelium after Chronic Spinal Cord Injury","volume":"45","author":"Khera","year":"2004","journal-title":"Neurochem. Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1124\/jpet.110.169342","article-title":"Excitatory Cholinergic and Purinergic Signaling in Bladder Are Equally Susceptible to Botulinum Neurotoxin a Consistent with Co-release of Transmitters from Efferent Fibers","volume":"334","author":"Lawrence","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1159\/000288223","article-title":"Current Information on Sacral Neuromodulation and Botulinum Toxin Treatment for Refractory Idiopathic Overactive Bladder Syndrome: a Review","volume":"84","author":"Leong","year":"2010","journal-title":"Urol. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"710","DOI":"10.13200\/j.cnki.cjb.001797","article-title":"Nonclinical Safety Evaluation of Botulinum Toxin Type A and Botulinum Neurotoxin Type A. (In Chinese)","volume":"30","author":"Liang","year":"2017","journal-title":"Chin. J. Biologicals"},{"key":"B22","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1097\/JU.0000000000000309","article-title":"Diagnosis and Treatment of Overactive Bladder (Non-neurogenic) in Adults: AUA\/SUFU Guideline Amendment 2019","volume":"202","author":"Lightner","year":"2019","journal-title":"J. Urol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1016\/j.juro.2012.12.022","article-title":"OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial","volume":"189","author":"Nitti","year":"2013","journal-title":"J. Urol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"S216","DOI":"10.1016\/j.juro.2016.10.109","article-title":"OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial","volume":"197","author":"Nitti","year":"2017","journal-title":"J. Urol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.juro.2016.03.146","article-title":"Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study","volume":"196","author":"Nitti","year":"2016","journal-title":"J. Urol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/WNF.0b013e3181c46f61","article-title":"Prospective, Randomized, Double-Blind Study, Comparing Botulinum Toxins Type a Botox and Prosigne for Blepharospasm and Hemifacial Spasm Treatment","volume":"33","author":"Quagliato","year":"2010","journal-title":"Clin. Neuropharmacol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/01.WNF.0000236771.77021.3C","article-title":"A Double-Blind, Randomized, Crossover Study of Prosigne versus Botox in Patients with Blepharospasm and Hemifacial Spasm","volume":"30","author":"Rieder","year":"2007","journal-title":"Clin. Neuropharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1111\/j.1742-1241.2010.02626.x","article-title":"Persistence and Adherence in the Treatment of Overactive Bladder Syndrome with Anticholinergic Therapy: a Systematic Review of the Literature","volume":"65","author":"Sexton","year":"2011","journal-title":"Int. J. Clin. Pract."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1002\/nau.21072","article-title":"Prevalence, Risk Factors, and Impact on Health Related Quality of Life of Overactive Bladder in China","volume":"30","author":"Wang","year":"2011","journal-title":"Neurourol Urodyn"},{"key":"B30","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/iju.14176","article-title":"OnabotulinumtoxinA (Botulinum Toxin Type A) for the Treatment of Japanese Patients with Overactive Bladder and Urinary Incontinence: Results of Single-Dose Treatment from a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial (Interim Analysis)","volume":"27","author":"Yokoyama","year":"2020","journal-title":"Int. J. Urol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"598","DOI":"10.13200\/j.cjb.2010.06.43.zhaoyj.010","article-title":"Cloning and Sequencing of Complete BoNT Gene of Clostridium Botulinum Type A for Therapy. (In Chinese)","volume":"23","author":"Zhao","year":"2010","journal-title":"Chin. J. Biologicals"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.840695\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T07:08:29Z","timestamp":1645168109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.840695\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":31,"alternative-id":["10.3389\/fphar.2022.840695"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.840695","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"article-number":"840695"}}