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.
RCT Entities:
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.
Authors: Gustavo E Velásquez; Meredith B Brooks; Julia M Coit; Henry Pertinez; Dante Vargas Vásquez; Epifanio Sánchez Garavito; Roger I Calderón; Judith Jiménez; Karen Tintaya; Charles A Peloquin; Elna Osso; Dylan B Tierney; Kwonjune J Seung; Leonid Lecca; Geraint R Davies; Carole D Mitnick Journal: Am J Respir Crit Care Med Date: 2018-09-01 Impact factor: 21.405
Authors: C A Peloquin; G E Velásquez; L Lecca; R I Calderón; J Coit; M Milstein; E Osso; J Jimenez; K Tintaya; E Sanchez Garavito; D Vargas Vasquez; C D Mitnick; G Davies Journal: Antimicrob Agents Chemother Date: 2017-07-25 Impact factor: 5.191
Authors: Till F Omansen; Deepak Almeida; Paul J Converse; Si-Yang Li; Jin Lee; Ymkje Stienstra; Tjip van der Werf; Jacques H Grosset; Eric L Nuermberger Journal: Antimicrob Agents Chemother Date: 2019-01-29 Impact factor: 5.191
Authors: R Court; M T Chirehwa; L Wiesner; B Wright; W Smythe; N Kramer; H McIlleron Journal: Int J Tuberc Lung Dis Date: 2018-05-01 Impact factor: 2.373