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Safety and Efficacy of 25 mg/kg and 35 mg/kg vs 10 mg/kg Rifampicin in Pulmonary TB: A Phase IIb Randomized Controlled Trial.

Authors :
Kannabiran, Bhavani Perumal
Palaniappan, Natarajan Alangudi
Manoharan, Tamizhselvan
Paramasivam, Paul Kumaran
Saini, Jitendra Kumar
Ansari, Mohammed Soheb
Jayabal, Lavanya
Aggarwal, Ashutosh N
Garg, Rajiv
Subramanyam, Balaji
Thakur, Deepika
Pantula, Shilpa
M, Ramesh P
GS, Vijayachandar
Natarajan, Saravanan
Ammayappan, Radha Krishnan
Manpreet, Bhalla
Ganesan, Mangalambal
Angamuthu, Dhanalakshmi
Chinnaiyan, Ponnuraja
Source :
Open Forum Infectious Diseases. Mar2024, Vol. 11 Issue 3, p1-11. 11p.
Publication Year :
2024

Abstract

Background Globally, no trial data are available on head-to-head comparison between 10 mg/kg and 25/35 mg/kg rifampicin in treating pulmonary tuberculosis during study initiation. Methods A multicentric, phase IIb randomized trial recruited 333 new culture-positive, drug-sensitive adult patients with pulmonary tuberculosis to compare safety and efficacy of high-dose rifampicin (R25/R35), against conventional dose (R10) given daily for 8 weeks followed by standard doses for 16 weeks. Main outcomes were treatment-emergent grade 3/4 adverse events (AEs) and time-to-culture conversion in liquid media, assessed by division of AIDS system for grading the severity of adverse events division of AIDS criteria and Kaplan-Meier methods. Results In a modified intention-to-treat population of 323 patients (R10: 105/R25: 112/R35: 106), grade 3/4 AEs were reported in 34 patients (R10: 9.5% [10/105], R25: 9.8% [11/112], R35: 12.3% [13/106]) during the intensive phase. Among 23 patients (R10: 3.8% [4/105], R25: 6.3% [7/112], R35: 11.3% [12/106]) with grade 3/4 hepatotoxicity, 15 (R10: 1.9% [2/105], R25: 3.6% [4/112], R35: 8.5% [9/106]) had grade 3/4 hyperbilirubinemia and 9 patients (R10: 1.0% [1/105], R25: 0.9% [1/112], R35: 6.6% [7/106]) developed clinical jaundice. Significant differences observed only between R10 and R35 with hepatotoxicity (P =.039), hyperbilirubinemia (P =.031), clinical jaundice (P =.032), and treatment interruption (P =.039). Eighteen serious AEs and 6 deaths (R10: 3/R25: 1/R35: 2) occurred during study period. Time to stable culture conversion in liquid media was faster in R25 (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.26–2.31 [solid: 1.97; 95% CI, 1.46–2.67]) and R35 (1.81; 95% CI, 1.33–2.48 [solid: 2.24; 95% CI, 1.64–3.06]), than R10 (34 vs 44 days). R25 had no failure/relapse. Conclusions Hepatotoxicity, clinical jaundice, and treatment interruptions occurred significantly higher with R35 than R10. Because R25 was comparably safe as R10 and also highly efficacious than R10, it may be considered for implementation. Clinical Trials Registration. CTRI/2017/12/010951. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
23288957
Volume :
11
Issue :
3
Database :
Academic Search Index
Journal :
Open Forum Infectious Diseases
Publication Type :
Academic Journal
Accession number :
176726229
Full Text :
https://doi.org/10.1093/ofid/ofae034