PMID- 38444824
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240420
IS  - 2328-8957 (Print)
IS  - 2328-8957 (Electronic)
IS  - 2328-8957 (Linking)
VI  - 11
IP  - 3
DP  - 2024 Mar
TI  - 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.
PG  - ofae034
LID - 10.1093/ofid/ofae034 [doi]
LID - ofae034
AB  - 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.
CI  - (c) The Author(s) 2024. Published by Oxford University Press on behalf of 
      Infectious Diseases Society of America.
FAU - Perumal Kannabiran, Bhavani
AU  - Perumal Kannabiran B
AUID- ORCID: 0000-0001-7385-139X
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Palaniappan, Natarajan Alangudi
AU  - Palaniappan NA
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Manoharan, Tamizhselvan
AU  - Manoharan T
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Paramasivam, Paul Kumaran
AU  - Paramasivam PK
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Saini, Jitendra Kumar
AU  - Saini JK
AD  - Department of Pulmonary Oncology, National Institute for Tuberculosis and 
      Respiratory Diseases, New Delhi, India.
FAU - Ansari, Mohammed Soheb
AU  - Ansari MS
AD  - Department of Respiratory Medicine, Bhagwan Mahavir Medical Hospital and Research 
      Centre, Hyderabad, India.
FAU - Jayabal, Lavanya
AU  - Jayabal L
AD  - District TB office, Greater Chennai Corporation, Chennai, India.
FAU - Aggarwal, Ashutosh N
AU  - Aggarwal AN
AD  - Department of Respiratory Medicine, Post Graduate Institute of Medical Research, 
      Chandigarh, India.
FAU - Garg, Rajiv
AU  - Garg R
AD  - Department of Respiratory Medicine, King George's Medical University, Lucknow, 
      India.
FAU - Subramanyam, Balaji
AU  - Subramanyam B
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Thakur, Deepika
AU  - Thakur D
AD  - Department of Respiratory Medicine, Post Graduate Institute of Medical Research, 
      Chandigarh, India.
FAU - Pantula, Shilpa
AU  - Pantula S
AD  - Department of Respiratory Medicine, Bhagwan Mahavir Medical Hospital and Research 
      Centre, Hyderabad, India.
FAU - P M, Ramesh
AU  - P M R
AD  - Department of Respiratory Medicine, Government Thiruvotteeswarar Hospital of 
      Thoracic Medicine, Chennai, India.
FAU - Gs, Vijayachandar
AU  - Gs V
AD  - Department of Respiratory Medicine, Institute of Thoracic Medicine, Chennai, 
      India.
FAU - Natarajan, Saravanan
AU  - Natarajan S
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Ammayappan, Radha Krishnan
AU  - Ammayappan RK
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Manpreet, Bhalla
AU  - Manpreet B
AD  - Department of Pulmonary Oncology, National Institute for Tuberculosis and 
      Respiratory Diseases, New Delhi, India.
FAU - Ganesan, Mangalambal
AU  - Ganesan M
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Angamuthu, Dhanalakshmi
AU  - Angamuthu D
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Chinnaiyan, Ponnuraja
AU  - Chinnaiyan P
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Singh, Manjula
AU  - Singh M
AD  - Division of Communicable Diseases, Indian Council of Medical Research, New Delhi, 
      India.
FAU - Chandrasekaran, Padmapriyadarsini
AU  - Chandrasekaran P
AD  - Department of Clinical Resarch, ICMR - National Institute for Research in 
      Tuberculosis, Chennai, India.
FAU - Swaminathan, Soumya
AU  - Swaminathan S
AD  - Former Chief Scientist, World Health Organisation, Geneva, Switzerland.
LA  - eng
GR  - 001/WHO_/World Health Organization/International
PT  - Clinical Trial
DEP - 20240202
PL  - United States
TA  - Open Forum Infect Dis
JT  - Open forum infectious diseases
JID - 101637045
PMC - PMC10914527
OTO - NOTNLM
OT  - efficacy
OT  - high-dose
OT  - rifampicin
OT  - safety
OT  - time-to-culture-conversion
COIS- Potential conflicts of interest. All authors: No reported conflicts.
EDAT- 2024/03/06 06:43
MHDA- 2024/03/06 06:44
PMCR- 2024/02/02
CRDT- 2024/03/06 03:55
PHST- 2023/08/18 00:00 [received]
PHST- 2024/01/24 00:00 [accepted]
PHST- 2024/03/06 06:44 [medline]
PHST- 2024/03/06 06:43 [pubmed]
PHST- 2024/03/06 03:55 [entrez]
PHST- 2024/02/02 00:00 [pmc-release]
AID - ofae034 [pii]
AID - 10.1093/ofid/ofae034 [doi]
PST - epublish
SO  - Open Forum Infect Dis. 2024 Feb 2;11(3):ofae034. doi: 10.1093/ofid/ofae034. 
      eCollection 2024 Mar.