Treatment for Prevention of Variceal Rebleeding Guided by the Hemodynamic Response - Full Text View

Sponsor:	Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Information provided by:	Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier:	NCT00563602

Purpose

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)

Condition	Intervention	Phase
Portal Hypertension Complications of Cirrhosis	Other: Hemodynamic guided therapy	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Cirrhosis Endoscopy High Blood Pressure

Drug Information available for: Isosorbide-5-mononitrate Nadolol Isosorbide dinitrate Isosorbide

U.S. FDA Resources

Further study details as provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:

Primary Outcome Measures:

Rebleeding [ Time Frame: 1-2 Years ]

Secondary Outcome Measures:

Survival [ Time Frame: 1-2 Years ]
Adverse effects [ Time Frame: 1-2 Years ]

Estimated Enrollment:	140
Study Start Date:	August 2007
Estimated Study Completion Date:	November 2007

Arms	Assigned Interventions
2: Active Comparator Standard Therapy: Endoscopic ligation (LEV) + Nadolol + Isosorbide mononitrate (MNI)(drugs carefully titrated until achieve maximum tolerated dose)	Other: 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)
1: Experimental 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)	Other: 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)

Arms

Assigned Interventions

2: Active Comparator

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

Other: 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)

1: Experimental

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)

Other: 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)

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)

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00563602

Contacts

Contact: Candid Villanueva, MD	+34620955006	cvillanueva@santpau.es
Contact: Jordi Virgili

Locations

Spain
HospitalSCSP	Recruiting
Barcelona, Spain, 08025
Contact: Candid Villanueva, MD +34620955006 cvillanueva@santpau.es
Principal Investigator: Candid Villanueva, MD

Sponsors and Collaborators

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

Investigators

Principal Investigator:

Candid Villanueva, MD

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

More Information

No publications provided

Study ID Numbers:	CONHEMO-2006, EudraCT 2007-002237-37
Study First Received:	November 21, 2007
Last Updated:	November 22, 2007
ClinicalTrials.gov Identifier:	NCT00563602 History of Changes
Health Authority:	Spain: Comité Ético de Investigación Clínica

Keywords provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:

Portal hypertension
Prevention of rebleeding
Complications of cirrhosis
Portal hemodynamic

Prazosine
Nadolol
isosorbide mononitrate
Prevention of rebleeding

Additional relevant MeSH terms:

Isosorbide
Neurotransmitter Agents
Liver Diseases
Vasodilator Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Isosorbide-5-mononitrate
Fibrosis
Diuretics
Physiological Effects of Drugs
Isosorbide Dinitrate
Liver Cirrhosis
Hypertension, Portal
Nitric Oxide Donors
Pathologic Processes

Therapeutic Uses
Adrenergic beta-Antagonists
Cardiovascular Diseases
Anti-Arrhythmia Agents
Sympatholytics
Diuretics, Osmotic
Vascular Diseases
Nadolol
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions
Digestive System Diseases
Autonomic Agents
Natriuretic Agents
Adrenergic Antagonists

ClinicalTrials.gov processed this record on November 09, 2009