Clinical trial NCT00563602: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Portal Hypertension
Complications of Cirrhosis
Keywords: Portal hypertension
Prevention of rebleeding
Complications of cirrhosis
Portal hemodynamic
Prazosine
Nadolol
isosorbide mononitrate
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
First posted: 2007-11-26
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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)

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.

Primary outcomes:
measure: Rebleeding
timeFrame: 1-2 Years
Secondary outcomes:
measure: Survival
timeFrame: 1-2 Years
measure: Adverse effects
timeFrame: 1-2 Years
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: HospitalSCSP
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Candid Villanueva, MD
role: PRINCIPAL_INVESTIGATOR
References: