Ando Naokatsu, Mizushima Daisuke, Shimizu Yosuke, Uemura Yukari, Takano Misao, Mitobe Morika, Kobayashi Kai, Kubota Hiroaki, Miyake Hirofumi, Suzuki Jun, Sadamasu Kenji, Nakamoto Takato, Aoki Takahiro, Watanabe Koji, Oka Shinichi, Gatanaga Hiroyuki
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
Biostatistics Section, Department of Data Science, National Center for Global Health and Medicine, Tokyo, Japan.
JMIR Res Protoc. 2023 Nov 14;12:e52565. doi: 10.2196/52565.
Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains.
This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections.
We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains.
Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate.
This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power.
Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52565.
生殖支原体是一种新出现的性传播病原体，与抗生素耐药性增加相关。当前的治疗指南推荐对大环内酯类耐药的生殖支原体或耐药情况未知的菌株采用莫西沙星序贯疗法。然而，尚不清楚第四代氟喹诺酮类抗生素西他沙星对耐药菌株是否有效。
本研究旨在评估和比较基于西他沙星和莫西沙星的治疗方案对生殖支原体感染的疗效和安全性。
我们将在日本的多个中心进行这项随机对照试验。符合条件的参与者包括18岁及以上经核酸扩增试验确诊为生殖支原体感染的成年人。患者将根据治疗机构和感染部位采用分层方法进行随机分组。干预措施包括每日口服西他沙星（200mg），共7天（可选择口服多西环素进行预处理，每日200mg，最多7天），对照组为每日口服多西环素（200mg），共7天，随后每日口服莫西沙星（400mg），再持续7天。主要结局是通过核酸扩增试验确认的治疗成功率，优效性界值为10%。次要结局包括泌尿生殖道或直肠部位细菌载量的变化以及治疗后耐药突变菌株的出现。
入组于2023年6月开始，将于2024年12月结束，预计2025年得出结果。根据以往研究，对于携带G248T（S83I）突变的生殖支原体，西他沙星的预期成功率在80%左右，莫西沙星为42%。因此，在5%的显著性水平（双侧）和80%的统计效能下，考虑到预期10%的脱落率，我们计划每组招募五十名参与者。
本研究将为基于西他沙星与莫西沙星的序贯疗法治疗生殖支原体感染的疗效和安全性提供有价值的见解。这些发现有可能影响临床指南，支持更有效的治疗选择。多中心方法增强了本研究的稳健性。然而，一个局限性是每组检测治疗后耐药突变菌株的统计效能可能不足，使得治疗后耐药突变成为一个值得关注的问题。未来，我们可能需要增加样本量以提高效能。
日本临床试验注册中心（jRCTs031230111）；https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111。
国际注册报告识别码（IRRID）：DERR1-10.2196/52565。
