Back to results

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

Primary Purpose

Liver Cirrhosis, Portal Hypertension

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Rifaximin + propranolol

Propranolol + Placebo

About this trial

This is an interventional treatment trial for Liver Cirrhosis focused on measuring Liver cirrhosis, Portal hypertension, Hepatic Venous Pressure Gradient, Rifaximin

Eligibility Criteria

19 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Yonsei University Wonju Severance Cristian Hospital
Wonju Severance Christian HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Combination therapy

Monotherapy

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

occurence of gastrointestinal bleeding

when gastrointestinal bleeding occurs, after initiation of treatment, endoscopy will be performed to evaluate status of bleeding

Full Information

NCT ID

NCT01897051

First Posted

July 1, 2013

Last Updated

April 19, 2015

Sponsor

Yonsei University

1. Study Identification

Unique Protocol Identification Number

NCT01897051

Brief Title

Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Unknown status

Study Start Date

July 2013 (undefined)

Primary Completion Date

February 2017 (Anticipated)

Study Completion Date

June 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Yonsei University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cirrhosis, Portal Hypertension

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Combination therapy

Arm Type

Experimental

Arm Description

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

Arm Title

Monotherapy

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rifaximin + propranolol

Other Intervention Name(s)

Normix, Propranolol

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Propranolol + Placebo

Other Intervention Name(s)

Non-selective beta-blocker, Placebo of Rifaximin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Hepatic vein pressure gradient(HVPG)

Description

Time Frame

Change from baseline heptic vein pressure gradient at 6 weeks

Secondary Outcome Measure Information:

Title

occurence of gastrointestinal bleeding

Description

when gastrointestinal bleeding occurs, after initiation of treatment, endoscopy will be performed to evaluate status of bleeding

Time Frame

upto 6 months after initiation of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Moon Young Kim, MD,PhD

Phone

82-33-741-1225

drkimmy@yonsei.ac.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Moon Young Kim, MD,PhD

Organizational Affiliation

Yonsei University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Moon Young Kim, M.D., PhD.

Organizational Affiliation

Yonsei University Wonhu College of Medicine Wonju Severance Christian Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Yonsei University Wonju Severance Cristian Hospital

City

Wonju

State/Province

Kangwon-do

ZIP/Postal Code

220-701

Country

Korea, Republic of

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Moon Young Kim, MD,PhD

Phone

82-33-741-1225

drkimmy@yonsei.ac.kr

First Name & Middle Initial & Last Name & Degree

Moon Young Kim, MD,PhD

Facility Name

Wonju Severance Christian Hospital

City

Wonju

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Moon Young Kim, MD., PhD.

12. IPD Sharing Statement

Citations:

PubMed Identifier

12899586

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.

Results Reference

background

PubMed Identifier

19210289

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.

Results Reference

background

PubMed Identifier

17006916

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.

Results Reference

background

PubMed Identifier

16175621

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.

Results Reference

background

PubMed Identifier

18433395

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.

Results Reference

background

Learn more about this trial

Rifaximin and Propranolol Combination Therapy Versus Propranolol Monotherapy in Cirrhotic Patients

We'll reach out to this number within 24 hrs