Treatment for Prevention of Variceal Rebleeding Guided by the Hemodynamic Response

NCT ID: NCT00563602

Last Updated: 2007-11-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2007-11-30

Brief Summary

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 + 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)

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)

Conditions

Portal Hypertension; Complications of Cirrhosis

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

2

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

Group Type: ACTIVE_COMPARATOR

Hemodynamic guided therapy

Intervention Type: OTHER

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)

1

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)

Group Type: EXPERIMENTAL

Hemodynamic guided therapy

Intervention Type: OTHER

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)

Interventions

Hemodynamic guided therapy

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)

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Principal Investigators

Candid Villanueva, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

HospitalSCSP

Barcelona, Barcelona, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Candid Villanueva, MD

Role: CONTACT

Phone: +34620955006

Email: cvillanueva@santpau.es

Jordi Virgili

Role: CONTACT

Facility Contacts

Candid Villanueva, MD

Role: primary

Other Identifiers

EudraCT 2007-002237-37

Identifier Type: -

Identifier Source: secondary_id

CONHEMO-2006

Identifier Type: -

Identifier Source: org_study_id