Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients

NCT ID: NCT01897051

Last Updated: 2015-04-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2017-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Combination therapy

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

Group Type: EXPERIMENTAL

Rifaximin + propranolol

Intervention Type: 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.

Monotherapy

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

Group Type: PLACEBO_COMPARATOR

Propranolol + Placebo

Intervention Type: 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.

Interventions

Rifaximin + 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.

Intervention Type: DRUG

Propranolol + 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.

Intervention Type: DRUG

Other Intervention Names

Normix; Propranolol; Non-selective beta-blocker; Placebo of Rifaximin

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Moon Young Kim

Associate Professor, Divistion of Gastroenterology and Hepatology, Department of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Moon Young Kim, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Yonsei University

Moon Young Kim, M.D., PhD.

Role: STUDY_CHAIR

Yonsei University Wonhu College of Medicine Wonju Severance Christian Hospital

Locations

Yonsei University Wonju Severance Cristian Hospital

Wŏnju, Gangwon-do, South Korea

Site Status: NOT_YET_RECRUITING

Wonju Severance Christian Hospital

Wŏnju, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Moon Young Kim, MD,PhD

Role: CONTACT

drkimmy@yonsei.ac.kr

82-33-741-1225

Facility Contacts

Moon Young Kim, MD,PhD

Role: primary

drkimmy@yonsei.ac.kr

82-33-741-1225

References

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.

Reference Type: BACKGROUND

PMID: 12899586 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19210289 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17006916 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16175621 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18433395 (View on PubMed)

Other Identifiers

CR310037

Identifier Type: -

Identifier Source: org_study_id