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Abstract Details
Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-Controlled Trials
Clin Gastroenterol Hepatol. 2022 Jun 21;S1542-3565(22)00595-X.doi: 10.1016/j.cgh.2022.05.042. Online ahead of print.
1Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia; Division of Gastroenterology, Central Virginia Veterans Affairs Healthcare System, Richmond, Virginia. Electronic address: jasmohan.bajaj@vcuhealth.org.
2Southern California Research Center, Coronado, California.
3Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey.
4Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia.
5Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Baylor Scott and White, Dallas, Texas.
6Salix Pharmaceuticals, Bridgewater, New Jersey.
7Medical University of South Carolina, Charleston, South Carolina.
Abstract
Background & aims: Cirrhosis-related complications are a major burden. Rifaximin soluble solid dispersion (SSD) tablets (immediate-release [IR]; sustained extended-release [SER]) were designed to increase rifaximin water solubility. These analyses evaluate dosing for prevention of cirrhosis complication-related hospitalizations/mortality and overt hepatic encephalopathy (OHE) treatment.
Methods: Two phase 2, randomized, double-blind, placebo-controlled trials were conducted. Trial 1: outpatients with early decompensated cirrhosis randomized to placebo or rifaximin SSD once-nightly: IR 40 or 80 mg, SER 40 or 80 mg, or IR 80 mg plus SER 80 mg, for 24 weeks. Trial 2: inpatients with OHE randomized to lactulose plus placebo or rifaximin SSD: IR 40 mg once or twice daily (qd/bid) or SER 80 mg qd/bid for ≤14 days. Primary efficacy endpoint: time to cirrhosis complication-related hospitalization/all-cause mortality (Trial 1) or time to OHE resolution (Trial 2).
Results: In Trial 1 (n = 516), no significant difference in time to cirrhosis complication-related hospitalization/all-cause mortality versus placebo. In a post hoc analysis, time to all-cause hospitalization/all-cause mortality was improved with IR 40 mg versus placebo (15.4% [12/78] vs 27.7% [26/94]; P = .03). A Trial 2 prespecified interim analysis (n = 71) showed lactulose plus rifaximin SSD IR 40 mg bid significantly reduced median time to OHE resolution (21.1 h) versus lactulose plus placebo (62.7 h; P = .02). Trial 2 was subsequently terminated.
Conclusion: Rifaximin SSD IR 40 mg may reduce hospitalizations in patients with cirrhosis and shorten duration of OHE during hospitalization-considered a negative finding, yet also hypothesis-generating (ClinicalTrials.gov NCT01904409; NCT03515044).