A Four-Month Gatifloxacin-Containing Regimen for Treating Tuberculosis
Autor: | Corinne S, Merle, Katherine, Fielding, Omou Bah, Sow, Martin, Gninafon, Mame B, Lo, Thuli, Mthiyane, Joseph, Odhiambo, Evans, Amukoye, Boubacar, Bah, Ferdinand, Kassa, Alimatou, N'Diaye, Roxana, Rustomjee, Bouke C, de Jong, John, Horton, Christian, Perronne, Charalambos, Sismanidis, Olivier, Lapujade, Piero L, Olliaro, Christian, Lienhardt, I, Zongo |
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Rok vydání: | 2014 |
Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty Tuberculosis TUBERCULOSE HUMAINE ESSAI CLINIQUE Antitubercular Agents Gatifloxacin Drug Administration Schedule law.invention TRAITEMENT MEDICAL Mycobacterium tuberculosis GATIFLOXACINE Randomized controlled trial FLUOROQUINOLONE law Internal medicine Isoniazid medicine Humans Tuberculosis Pulmonary Ethambutol Intention-to-treat analysis biology business.industry General Medicine biology.organism_classification medicine.disease Pyrazinamide Intention to Treat Analysis Surgery Clinical trial ANTIBIOTIQUE Regimen BACTERIOSE EFFET INDESIRABLE Drug Therapy Combination Female Rifampin business Fluoroquinolones medicine.drug |
Zdroj: | New England Journal of Medicine. 371:1588-1598 |
ISSN: | 1533-4406 0028-4793 |
Popis: | BACKGROUND : Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS : We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS : A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P = 0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P = 0.04 for interaction) and body-mass index (P = 0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS : Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.) |
Databáze: | OpenAIRE |
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