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A randomised Phase II trial to evaluate the toxicity of high dose rifampicin to treat pulmonary tuberculosis

Jindani, A; Borgulya, G; de Patiño, IW; Gonzales, T; de Fernandes, RA; Shrestha, B; Atwine, D; Bonnet, C; Burgos, M; Dubash, F; et al. Jindani, A; Borgulya, G; de Patiño, IW; Gonzales, T; de Fernandes, RA; Shrestha, B; Atwine, D; Bonnet, C; Burgos, M; Dubash, F; Patel, N; Checkley, AM; Harrison, TS; Mitchison, DA (2016) A randomised Phase II trial to evaluate the toxicity of high dose rifampicin to treat pulmonary tuberculosis. INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, 20 (6). pp. 832-838. ISSN 1027-3719
SGUL Authors: Jindani, Amina

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Abstract

SETTING: Randomised Phase IIB clinical trial. OBJECTIVES: To assess whether increasing the dose of rifampicin (RMP) from 10 mg/kg to 15 or 20 mg/kg results in an increase in grade 3 or 4 hepatic adverse events and/or serious adverse events (SAE). METHODS: Three hundred human immunodeficiency virus negative patients with newly diagnosed microscopy-positive pulmonary tuberculosis (TB) were randomly assigned to one of three regimens: 1) the control regimen (R10), comprising daily ethambutol (EMB), isoniazid (INH), RMP and pyrazinamide for 8 weeks, followed by INH and RMP daily for 18 weeks; 2) Study Regimen 1 (R15), as above, with the RMP dose increased to 15 mg/kg body weight daily for the first 16 weeks; and 3) Study Regimen 2 (R20), as above, with RMP increased to 20 mg/kg. Serum alanine transferase (ALT) levels were measured at regular intervals. RESULTS: There were seven grade 3 increases in ALT levels, 1/100 (1%) among R10 arm patients, 2/100 (2%) in the R15 arm and 4/100 (4%) in the R20 arm (trend test P = 0.15). One (R15) patient developed jaundice, requiring treatment modification. There were no grade 4 ALT increases. There was a non-significant increase in culture negativity at 8 weeks with increasing RMP dosage: 75% (69/92) in R10, 82.5% (66/80) in R15 and 83.1% (76/91) R20 patients (P = 0.16). CONCLUSIONS: No significant increase in adverse events occurred when the RMP dose was increased from 10 mg/kg to 15 mg/kg or 20 mg/kg.

Item Type: Article
Additional Information: © 2016 International Union Against Tuberculosis and Lung Disease
Keywords: Microbiology, 1102 Cardiovascular Medicine And Haematology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
ISSN: 1027-3719
Dates:
DateEvent
1 June 2016Published
13 January 2016Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
UNSPECIFIEDSt. George's, University of LondonUNSPECIFIED
URI: https://openaccess.sgul.ac.uk/id/eprint/107620

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