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Treatment for Prevention of Variceal Rebleeding Guided by the Hemodynamic Response

Primary Purpose

Portal Hypertension, Complications of Cirrhosis

Status

Unknown status

Phase

Phase 4

Locations

Spain

Study Type

Interventional

Intervention

Hemodynamic guided therapy

About this trial

This is an interventional prevention trial for Portal Hypertension focused on measuring Portal hypertension, Prevention of rebleeding, Complications of cirrhosis, Portal hemodynamic, Prazosine, Nadolol, isosorbide mononitrate

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All the patients admitted in emergencies in which 1) with gastrointestinal bleeding due to esophageal varices assessed by endoscopy, will be included.
We define esophagic variceal bleeding as the endoscopic finding of any the following signs: 1) active variceal bleeding 2) clot or platelet cluster or 3 ) esophageal varices associated to red blood in esophagogastric lumen in the absence of other sources of bleeding.
Clinical criteria and / or analytical, ultrasound and / or liver biopsy consistent with the diagnosis of liver cirrhosis.
Written informed consent to participate in the study.
Patients in fertile age should use barrier methods to prevent pregnancy during the entire study. The pregnancy test prior to the study must be negative

Exclusion Criteria:

Age <18 or> 80 years.
Patients not eligible for active treatment due to any underlying morbid condition (terminals). Here are included those patients with advanced liver disfunction (Child-Pugh >) or any patient with life expectancy < 6 mo.
Refuse to participate in the study.
Bleeding due to causes other than the esophageal varices.
Prior inclusion in this study.
Failure in the control of the acute bleeding (index episode).
Pretreatment through elective LEV program, sclerotherapy or combined β- blockers plus nitrates, or portosystemic shunt (surgical or percutaneous).
Contraindication for β- blockers and MNI (not exclude patients with contraindication for one of these drugs) or endoscopic procedures.
Pregnancy.
Presence multiple hepatocellular carcinoma or only diameter > 5 cm.
Portal vein thrombosis.

Sites / Locations

HospitalSCSPRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm Description

Standard Therapy: Endoscopic ligation (LEV) + Nadolol + Isosorbide mononitrate (MNI)(drugs carefully titrated until achieve maximum tolerated dose)

Hemodynamic guided therapy: 1) LEV + Nadolol. HVPG measurement: if response, no changes, if not, switch to 2) LEV + Nadolol + MNI. HVPG measurement: if response, no changes, if not, switch to: 3) LEV + Nadolol + Prazosin. (drugs carefully titrated until achieve maximum tolerated dose)

Outcomes

Primary Outcome Measures

Rebleeding

Secondary Outcome Measures

Survival

Adverse effects

Full Information

NCT ID

NCT00563602

First Posted

November 21, 2007

Last Updated

November 22, 2007

Sponsor

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

1. Study Identification

Unique Protocol Identification Number

NCT00563602

Brief Title

Treatment for Prevention of Variceal Rebleeding Guided by the Hemodynamic Response

Official Title

Randomized and Controlled Study of Endoscopic Ligation, Nadolol and Isosorbide Mononitrate vs Endoscopic Ligation and Nadolol Alone, or Associated With Isosorbide Mononitrate or Prazosin, Depending of the Hemodinamyc Response

Study Type

Interventional

2. Study Status

Record Verification Date

November 2007

Overall Recruitment Status

Unknown status

Study Start Date

August 2007 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

November 2007 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Detailed Description

This is a prospective trial of random distribution, open, parallel group, in which patients with esophagic variceal bleeding will be randomized into two treatment groups, after controlling acute bleeding. All patients received standard medical therapy with b-blockers and endoscopic ligation (LEV) of esophageal varices. The control group will be assigned to receive LEV + Nadolol (N) + Isosorbide Mononitrate (MNI) The experimental group will be assigned to receive treatment according to the hemodynamic response. All patients included in the experimental group received LEV and pharmacological treatment nadolol alone or combined with MNI or Prazosin (PZ) A hepatic hemodynamic study will be performed to patients in both groups, at baseline (In which basal values and acute b-blockers response will be assessed), and a second study at the 3 rd -4 th week after the drug therapy start, after the titration of the doses. In the experimental group, responders to the acute administration of b-blockers will receive LEV + Nadolol alone, and those patients with no response will receive LEV + N + MNI, and another hemodynamic study will be performed 3 rd -4 th week after the drug therapy start, after the titration of the doses, to assess response. The non-responders in this control study will switched to LEV+ N + PZ, and a 3erd hemodynamic study will be performed. Randomization will be stratified according to the degree of hepatic insufficiency, assessed by the Child-Pugh classification (classes A and B vs C)

6. Conditions and Keywords

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

Portal Hypertension, Complications of Cirrhosis

Keywords

Portal hypertension, Prevention of rebleeding, Complications of cirrhosis, Portal hemodynamic, Prazosine, Nadolol, isosorbide mononitrate

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Standard Therapy: Endoscopic ligation (LEV) + Nadolol + Isosorbide mononitrate (MNI)(drugs carefully titrated until achieve maximum tolerated dose)

Arm Title

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Hemodynamic guided therapy

Intervention Description

To switch two or more different treatments for the prevention of variceal rebleeding according to the hemodynamic response. All patients in the experimental group will begin by: 1) LEV + Nadolol. HVPG measurement: if response, no changes, if not, switch to 2) LEV + Nadolol + MNI. HVPG measurement: if response, no changes, if not, switch to: 3) LEV + Nadolol + Prazosin. (drugs carefully titrated until achieve maximum tolerated dose)

Primary Outcome Measure Information:

Title

Rebleeding

Time Frame

1-2 Years

Secondary Outcome Measure Information:

Title

Survival

Time Frame

1-2 Years

Title

Adverse effects

Time Frame

1-2 Years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All the patients admitted in emergencies in which 1) with gastrointestinal bleeding due to esophageal varices assessed by endoscopy, will be included. We define esophagic variceal bleeding as the endoscopic finding of any the following signs: 1) active variceal bleeding 2) clot or platelet cluster or 3 ) esophageal varices associated to red blood in esophagogastric lumen in the absence of other sources of bleeding. Clinical criteria and / or analytical, ultrasound and / or liver biopsy consistent with the diagnosis of liver cirrhosis. Written informed consent to participate in the study. Patients in fertile age should use barrier methods to prevent pregnancy during the entire study. The pregnancy test prior to the study must be negative Exclusion Criteria: Age <18 or> 80 years. Patients not eligible for active treatment due to any underlying morbid condition (terminals). Here are included those patients with advanced liver disfunction (Child-Pugh >) or any patient with life expectancy < 6 mo. Refuse to participate in the study. Bleeding due to causes other than the esophageal varices. Prior inclusion in this study. Failure in the control of the acute bleeding (index episode). Pretreatment through elective LEV program, sclerotherapy or combined β- blockers plus nitrates, or portosystemic shunt (surgical or percutaneous). Contraindication for β- blockers and MNI (not exclude patients with contraindication for one of these drugs) or endoscopic procedures. Pregnancy. Presence multiple hepatocellular carcinoma or only diameter > 5 cm. Portal vein thrombosis.

Central Contact Person:

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

Candid Villanueva, MD

Phone

+34620955006

cvillanueva@santpau.es

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

Jordi Virgili

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Candid Villanueva, MD

Organizational Affiliation

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Official's Role

Principal Investigator

Facility Information:

Facility Name

HospitalSCSP

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Candid Villanueva, MD

Phone

+34620955006

cvillanueva@santpau.es

First Name & Middle Initial & Last Name & Degree

Candid Villanueva, MD

12. IPD Sharing Statement

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Treatment for Prevention of Variceal Rebleeding Guided by the Hemodynamic Response

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