Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients (RECOVER)

April 19, 2015 updated by: Moon Young Kim, Yonsei University

Hemodynamic Response of Rifaximin and Non-selective β-blocker Combination Therapy Versus Non-selective β-blocker Monotherapy in Cirrhotic Patients With Esophageal Varices

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

140

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Wonju, Korea, Republic of
        • Recruiting
        • Wonju Severance Christian Hospital
        • Principal Investigator:
          • Moon Young Kim, MD., PhD.
    • Kangwon-do
      • Wonju, Kangwon-do, Korea, Republic of, 220-701
        • Not yet recruiting
        • Yonsei University Wonju Severance Cristian Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Combination therapy
Rifaximin(normix®)+nonselective beta-blocker(Propranolol)
Drug: 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.

Other Names:
  • Propranolol
  • Normix
PLACEBO_COMPARATOR: Monotherapy
nonselective beta-blocker(Propranolol) + Placebo(of Rifaximin)
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.

Other Names:
  • Non-selective beta-blocker
  • Placebo of Rifaximin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic vein pressure gradient(HVPG)
Time Frame: 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
Change from baseline heptic vein pressure gradient at 6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
occurence of gastrointestinal bleeding
Time Frame: upto 6 months after initiation of treatment
when gastrointestinal bleeding occurs, after initiation of treatment, endoscopy will be performed to evaluate status of bleeding
upto 6 months after initiation of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yonsei University

Investigators

  • Principal Investigator: Moon Young Kim, MD,PhD, Yonsei University
  • Study Chair: Moon Young Kim, M.D., PhD., Yonsei University Wonhu College of Medicine Wonju Severance Christian Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (ANTICIPATED)

February 1, 2017

Study Completion (ANTICIPATED)

June 1, 2017

Study Registration Dates

First Submitted

July 1, 2013

First Submitted That Met QC Criteria

July 8, 2013

First Posted (ESTIMATE)

July 11, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

April 21, 2015

Last Update Submitted That Met QC Criteria

April 19, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR310037

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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