Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients

Yonsei University140 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

140

Conditions

Liver Cirrhosis Portal Hypertension

Interventions

1. Rifaximin : taking 400mg three times a day in the study period (total 1,200 mg per day) 2. 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.

Propranolol + PlaceboDRUG

1. Placebo of Rifaximin : taking 400mg three times a day in the study period (total 1,200 mg per day) 2. 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.

Eligibility

Sex: ALLMin age: 19 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (2)

Yonsei University Wonju Severance Cristian Hospital

Wŏnju, Gangwon-do, South Korea

NOT_YET_RECRUITING

Wonju Severance Christian Hospital

Wŏnju, South Korea

RECRUITING

Outcomes

Primary Outcomes

Hepatic vein pressure gradient(HVPG)

After measurement of baseline HVPG, patients will be randomized to treatment group of Rifaximin + Propranolol or Propranolol + Placebo. And 6 weeks after treatment, follow-up measurement of HVPG will be performed to evaluate efficacy of two regimens

Time frame: Change from baseline heptic vein pressure gradient at 6 weeks

Secondary Outcomes

occurence of gastrointestinal bleeding

when gastrointestinal bleeding occurs, after initiation of treatment, endoscopy will be performed to evaluate status of bleeding

Time frame: upto 6 months after initiation of treatment