Liver Cirrhosis | Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients
Liver Cirrhosis research study
What is the primary objective of this study?
To reduce portal pressure, the only recommended medication is nonselective beta blocker(NSBB). However, NSBB has some limitation to apply clinically because of poor response rate and compliance. Recent literature has supported the role of bacterial translocation as a mediator of splanchnic vasodilatation and portal hypertension. This stimulates the release of pro-inflammatory cytokines and the activation of the vasodilator NO resulting in a more pronounced deterioration of the baseline hyperdynamic circulatory state. Selective gut decontamination with Rifaximin can induce inhibition of bacterial translocation and associated worsening of portal hypertension. The investigators hypothesized that Rifaximin plus NSBB could result in decrease of portal pressure in cirrhotic patients with esophageal varices.
Who is eligible to participate?
Inclusion Criteria: - Liver cirrhosis:diagnosed based on histology or unequivocal clinical, sonographic, and laboratory findings - 19≤age≤75 - Hepatic venous pressure gradient > 12 mmHg - Informed consent Exclusion Criteria: - Shock status requiring vasopressor - Active infection, for example Spontaneous bacterial peritonitis - Acute renal failure patients of any cause - Clinically relevant coronary artery disease(NYHA functional angina classification III/IV),congestive heart failure NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the past 12 months - Poorly controlled hypertension (BP 150/100mmHg) - Hepatocellular carcinoma - History of another primary malignancy ≤ 3years - Medical or psychological conditions that would not permit the subject to complete thte study or sign informed consent - Pregnancy or lactation period - Serum creatinine ≧ 6mg/dL - Involvement in the conduct of other study within 30 days - Known hypersensitivity to Rifaximin or propranolol - Dysarrhythmia, inappropriate for study on investigator's judgment
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Rifaximin + propranololRifaximin : taking 400mg three times a day in the study period (total 1,200 mg per day) Propranolol : taking 40mg twice a day to start. If patient is tolerable and systolic blood pressure is above 90 mmHg, the dosage can be increased by doubling to every other day upto the 360mg per day. (Target heart rate : 25% reduction in baseline heart rate or at least 55 times per minute). If patient is not tolerable, we can reduce the dosage step-by-step until the adverse symptoms is disappeared.
Drug:Propranolol + PlaceboPlacebo of Rifaximin : taking 400mg three times a day in the study period (total 1,200 mg per day) Propranolol : taking 40mg twice a day to start. If patient is tolerable and systolic blood pressure is above 90 mmHg, the dosage can be increased by doubling to every other day upto the 360mg per day. (Target heart rate : 25% reduction in baseline heart rate or at least 55 times per minute). If patient is not tolerable, we can reduce the dosage step-by-step until the adverse symptoms is disappeared.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Combination therapyRifaximin(normix®)+nonselective beta-blocker(Propranolol)
Monotherapynonselective beta-blocker(Propranolol) + Placebo(of Rifaximin)
Start Date: July 2013
Completed Date: June 2017
Phase: Phase 2/Phase 3
Primary Outcome: Hepatic vein pressure gradient(HVPG)
Secondary Outcome: occurence of gastrointestinal bleeding
Study sponsors, principal investigator, and references
Principal Investigator: Moon Young Kim, MD,PhD
Lead Sponsor: Yonsei University
Rasaratnam B, Kaye D, Jennings G, Dudley F, Chin-Dusting J. The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial. Ann Intern Med. 2003 Aug 5;139(3):186-93.