Clinical trial NCT01897051: Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients
Official title: Hemodynamic Response of Rifaximin and Non-selective β-blocker Combination Therapy Versus Non-selective β-blocker Monotherapy in Cirrhotic Patients With Esophageal Varices
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Liver Cirrhosis
Portal Hypertension
Keywords: Liver cirrhosis
Portal hypertension
Hepatic Venous Pressure Gradient
Rifaximin
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2013-07-11
Enrollment: 140
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Hepatic vein pressure gradient(HVPG)
timeFrame: Change from baseline heptic vein pressure gradient at 6 weeks
Secondary outcomes:
measure: occurence of gastrointestinal bleeding
timeFrame: upto 6 months after initiation of treatment
Other outcomes:
Locations:
city: Wonju
country: Korea, Republic of
facility: Yonsei University Wonju Severance Cristian Hospital
state: Kangwon-do
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
Study officials:
affiliation: Yonsei University
name: Moon Young Kim, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yonsei University Wonhu College of Medicine Wonju Severance Christian Hospital
name: Moon Young Kim, M.D., PhD.
role: STUDY_CHAIR
References:
citation: 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. doi: 10.7326/0003-4819-139-3-200308050-00008.
citation: Vlachogiannakos J, Saveriadis AS, Viazis N, Theodoropoulos I, Foudoulis K, Manolakopoulos S, Raptis S, Karamanolis DG. Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis. Aliment Pharmacol Ther. 2009 May 1;29(9):992-9. doi: 10.1111/j.1365-2036.2009.03958.x. Epub 2009 Feb 7.
citation: Gonzalez A, Augustin S, Perez M, Dot J, Saperas E, Tomasello A, Segarra A, Armengol JR, Malagelada JR, Esteban R, Guardia J, Genesca J. Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study. Hepatology. 2006 Oct;44(4):806-12. doi: 10.1002/hep.21343.
citation: Ripoll C, Banares R, Rincon D, Catalina MV, Lo Iacono O, Salcedo M, Clemente G, Nunez O, Matilla A, Molinero LM. Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era. Hepatology. 2005 Oct;42(4):793-801. doi: 10.1002/hep.20871.
citation: Kumar M, Kumar A, Hissar S, Jain P, Rastogi A, Kumar D, Sakhuja P, Sarin SK. Hepatic venous pressure gradient as a predictor of fibrosis in chronic liver disease because of hepatitis B virus. Liver Int. 2008 May;28(5):690-8. doi: 10.1111/j.1478-3231.2008.01711.x.