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利福平用药4个月或异烟肼用药9个月治疗成人潜伏性结核
Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults


Dick Menzies ... 呼吸系统疾病 • 2018.08.02
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摘要


背景

9个月异烟肼用药方案可以预防潜伏性结核感染患者的活动性结核病。然而,该方案与依从率低和毒性作用相关。

 

方法

在一项在9个国家开展的开放标签试验中,我们将潜伏性结核感染成人患者随机分组,使其分别接受利福平4个月方案或异烟肼9个月方案治疗,以预防在随机分组后28个月内出现确诊的活动性结核病。研究评估了非劣效性和潜在的优效性。次要结局包括临床诊断的活动性结核病、3~5级不良事件以及完成治疗方案。结局由独立评估专家组裁定。

 

结果

在利福平组3,443例患者中,在7,732人-年随访期间,4例患者出现了确诊的活动性结核病,4例患者出现了临床诊断的活动性结核病,相比之下,在异烟肼组3,416例患者中,在7,652人-年随访期间,分别有4例和5例患者出现了确诊的和临床诊断的活动性结核病。确诊的活动性结核病的率差(利福平-异烟肼)低于0.01例/100人-年(95%置信区间[CI],-0.14~0.16),确诊或临床诊断的结核病的率差低于0.01例/100人-年(95% CI,-0.23~0.22)。结核病确诊病例和结核病确诊或临床诊断病例的率差的95% CI上限低于累积发生率的预设非劣效性界值(0.75个百分点);利福平方案不优于异烟肼方案。治疗完成率的差异为15.1个百分点(95% CI,12.7~17.4)。对于所有事件和肝毒性事件,146日(利福平方案的计划治疗持续时间[4个月]的120%)内发生的3~5级不良事件的率差分别为-1.1个百分点(95% CI,-1.9~-0.4)和-1.2个百分点(95% CI,-1.7~-0.7)。

 

结论

对于活动性结核病的预防,利福平4个月治疗方案不劣于异烟肼9个月治疗方案,并且前者与较高的治疗完成率和较好的安全性相关(由加拿大卫生研究院[Canadian Institutes of Health Research]、澳大利亚国家健康与医学研究委员会[Australian National Health and Medical Research Council]资助;在ClinicalTrials.gov注册号为NCT00931736)。





作者信息

Dick Menzies, M.D., Menonli Adjobimey, M.D., M.P.H., Rovina Ruslami, M.D., Ph.D., Anete Trajman, M.D., Ph.D., Oumou Sow, M.D., Heejin Kim, M.D., Joseph Obeng Baah, M.D., Guy B. Marks, Ph.D., F.R.A.C.P., Richard Long, M.D., Vernon Hoeppner, M.D., Kevin Elwood, M.D., Hamdan Al-Jahdali, M.D., Martin Gninafon, M.D., Lika Apriani, M.D., Raspati C. Koesoemadinata, M.D., Afranio Kritski, M.D., Ph.D., Valeria Rolla, M.D., Ph.D., Boubacar Bah, M.D., Alioune Camara, M.D., Ph.D., Isaac Boakye, B.Sc., Victoria J. Cook, M.D., Hazel Goldberg, M.B., B.S., Chantal Valiquette, C.N.A., Karen Hornby, M.Sc., Marie-Josée Dion, B.Sc., Pei-Zhi Li, M.Sc., Philip C. Hill, M.D., M.P.H., Kevin Schwartzman, M.D., M.P.H., and Andrea Benedetti, Ph.D.
From the Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre Research Institute (D.M., A.T., C.V., K.H., M.-J.D., P.Z.L., K.S., A.B.), and the Department of Epidemiology and Biostatistics (D.M., A.B.), McGill University, Montreal, the Faculty of Medicine and Dentistry, University of Alberta, Edmonton (R.L.), the Faculty of Medicine, University of Saskatchewan, Saskatoon (V.H.), and the BC Centre for Disease Control and the University of British Columbia, Vancouver (K.E., V.J.C.) — all in Canada; Centre National Hospitalier Universitaire de Pneumo-Phtisiologie, Cotonou, Benin (M.A., M.G.); the Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia (R.R., L.A., R.C.K.); State University of Rio de Janeiro (A.T.), Programa Academico de Tuberculose–Faculdade de Medicina, Universidade Federal do Rio de Janeiro–Rede TB (A.K.), and National Institute of Infectious Diseases Evandro Chagas (V.R.) — all in Rio de Janeiro; Service de Pneumophtisiologie, Hôpital National Ignace Deen, Université Gamal Abdel Nasser de Conakry, Conakry, Guinea (O.S., B.B., A.C.); Korean Institute of Tuberculosis, Seoul, South Korea (H.K.); Komfo Anokye Teaching Hospital, Kumasi, Ghana (J.O.B., I.B.); University of New South Wales (G.B.M.) and University of Sydney (H.G.), Sydney; Centre for International Health, University of Otago, Dunedin, New Zealand (P.C.H.); and the Department of Medicine, King Saud University, King Abdulaziz Medical City, Riyadh, Saudi Arabia (H.A.-J.). Address reprint requests to Dr. Menzies at the Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre Research Institute, 5252 Blvd. de Maisonneuve Ouest, Office 3.58, Montreal, QC H4A 3S5, Canada, or at dick.menzies@mcgill.ca.

 

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