A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis
Andrew NunnFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofPatrick PhillipsFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofSarah MeredithFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofChen‐Yuan ChiangFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofFrancesca ConradieFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofD. DalaiFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofArmand Van DeunFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofPhan-Thuong DatFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofNgoc LanFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofIqbal MasterFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofTesfamarium MebrahtuFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofDaniel MeressaFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofRonelle MoodliarFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofNosipho NgubaneFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofKaren SandersFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofS. Bertel SquireFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofGabriela TorreaFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofBazarragchaa TsogtFrom the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), London (A.J.N, P.P.J.P., S.K.M., K.S.), and the Liverpool School of Tropical Medicine, Liverpool (S.B.S.) — both in the United Kingdom; International Union against Tuberculosis and Lung Disease (the Union), Paris (C.-Y.C., A.D., I.D.R.); the Department of Internal Medicine, Wanfang Hospital, and School of Medicine, Taipei Medical University (C.-Y.C.) — both in Taipei, Taiwan; the University ofI. D. RusenUniversity College London
2019en
ABI
Аннотация
BACKGROUND: Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS: at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS: Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], -7.5 to 9.5) (P = 0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, -10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONS: In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.).
Перевод пока недоступен
Идентификаторы
Цитирования и источники
Цитирований: 6Использованных источников: 0