Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients

Liver Cirrhosis Clinical Trial

— RECOVER  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01897051
• Other study ID #: CR310037
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: July 1, 2013
• Last updated: April 19, 2015
• Start date: July 2013
• Est. completion date: June 2017

Study information

• Verified date: April 2015
• Source: Yonsei University
• Contact: Moon Young Kim, MD,PhD
• Phone: 82-33-741-1225
• Email: drkimmy[@]yonsei.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationKorea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: June 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Wonju Severance Christian Hospital	Wonju
Korea, Republic of	Yonsei University Wonju Severance Cristian Hospital	Wonju	Kangwon-do

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (5)

González A, Augustin S, Pérez M, Dot J, Saperas E, Tomasello A, Segarra A, Armengol JR, Malagelada JR, Esteban R, Guardia J, Genescà J. Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study. Hepatology. 2006 Oct;44(4):806-12. — View 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. — View 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. — View Citation

Ripoll C, Bañares R, Rincón D, Catalina MV, Lo Iacono O, Salcedo M, Clemente G, Núñez 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	occurence of gastrointestinal bleeding	when gastrointestinal bleeding occurs, after initiation of treatment, endoscopy will be performed to evaluate status of bleeding	upto 6 months after initiation of treatment	Yes