Kevin D Mullen1, Arun J Sanyal2, Nathan M Bass3, Fred F Poordad4, Muhammad Y Sheikh5, R Todd Frederick6, Enoch Bortey7, William P Forbes7. 1. Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: kdm@case.edu. 2. Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia. 3. Divison of Gastroenterology, University of California San Francisco, San Francisco, California. 4. The Texas Liver Institute/University of Texas Health Science Center, San Antonio, Texas. 5. University of California San Francisco Fresno Medical Education Program, Fresno, California. 6. Division of Hepatology, California Pacific Medical Center, San Francisco, California. 7. Salix Pharmaceuticals, Inc, Raleigh, North Carolina.
Abstract
BACKGROUND & AIMS:Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. METHODS: We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140). RESULTS: In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). CONCLUSIONS: Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.
RCT Entities:
BACKGROUND & AIMS:Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. METHODS: We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140). RESULTS: In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). CONCLUSIONS: Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.
Authors: E Bouza; L Alcalá; M Marín; M Valerio; E Reigadas; P Muñoz; M González-Del Vecchio; V de Egea Journal: Eur J Clin Microbiol Infect Dis Date: 2017-05-13 Impact factor: 3.267
Authors: Jasmohan S Bajaj; Jacqueline G O'Leary; Puneeta Tandon; Florence Wong; Patrick S Kamath; Scott W Biggins; Guadalupe Garcia-Tsao; Jennifer Lai; Michael B Fallon; Paul J Thuluvath; Hugo E Vargas; Benedict Maliakkal; Ram M Subramanian; Leroy R Thacker; K Rajender Reddy Journal: Aliment Pharmacol Ther Date: 2019-04-29 Impact factor: 8.171