Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients

NCT01897051 | Unknown Phase 2

• 1 other identifier: CR310037
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

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.

Conditions

Liver Cirrhosis; Portal Hypertension

Keywords

Liver cirrhosis; Portal hypertension; Hepatic Venous Pressure Gradient; Rifaximin

Outcome Measures

Primary Outcomes (1)

• 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

  Change from baseline heptic vein pressure gradient at 6 weeks

Secondary Outcomes (1)

• occurence of gastrointestinal bleeding

  upto 6 months after initiation of treatment

Study Arms (2)

Combination therapy

EXPERIMENTAL

Rifaximin(normix®)+nonselective beta-blocker(Propranolol)

Drug: Rifaximin + propranolol

Monotherapy

PLACEBO COMPARATOR

nonselective beta-blocker(Propranolol) + Placebo(of Rifaximin)

Drug: Propranolol + Placebo

Interventions

Rifaximin + propranolol DRUG

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.

Also known as: Normix, Propranolol

Combination therapy

Propranolol + Placebo DRUG

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.

Also known as: Non-selective beta-blocker, Placebo of Rifaximin

Monotherapy

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver cirrhosis:diagnosed based on histology or unequivocal clinical, sonographic, and laboratory findings
• ≤age≤75
• Hepatic venous pressure gradient \> 12 mmHg
• Informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (2)

Yonsei University Wonju Severance Cristian Hospital

Wŏnju, Gangwon-do, 220-701, South Korea

NOT YET RECRUITING

Wonju Severance Christian Hospital

Wŏnju, South Korea

RECRUITING

Related Publications (5)

• 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.

  PMID: 12899586 BACKGROUND

• 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.

  PMID: 19210289 BACKGROUND

• 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.

  PMID: 17006916 BACKGROUND

• 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.

  PMID: 16175621 BACKGROUND

• 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.

  PMID: 18433395 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Interventions

Rifaximin; Propranolol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Moon Young Kim, MD,PhD

  Yonsei University

  PRINCIPAL INVESTIGATOR

• Moon Young Kim, M.D., PhD.

  Yonsei University Wonhu College of Medicine Wonju Severance Christian Hospital

  STUDY CHAIR

Central Study Contacts

Moon Young Kim, MD,PhD

CONTACT

82-33-741-1225; drkimmy@yonsei.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Divistion of Gastroenterology and Hepatology, Department of Internal Medicine

Study Record Dates

• First Submitted: July 1, 2013
• First Posted: July 11, 2013
• Study Start: July 1, 2013
• Primary Completion: February 1, 2017
• Study Completion: June 1, 2017
• Last Updated: April 21, 2015

Record last verified: 2015-04

Locations

KR (2)