Liver Cirrhosis, Portal Hypertension
Conditions
Keywords
Liver cirrhosis, Portal hypertension, Hepatic Venous Pressure Gradient, Rifaximin
Brief summary
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.
Interventions
DRUGRifaximin + propranolol
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.
DRUGPropranolol + Placebo
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.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic vein pressure gradient(HVPG) | Change from baseline heptic vein pressure gradient at 6 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| occurence of gastrointestinal bleeding | upto 6 months after initiation of treatment | when gastrointestinal bleeding occurs, after initiation of treatment, endoscopy will be performed to evaluate status of bleeding |
Countries
South Korea
Contacts
Primary ContactMoon Young Kim, MD,PhD
Outcome results
None listed