A randomized phase IV clinical trial comparing Nadolol and Isosorbide Mononitrate (ISMN) with the combination of Endoscopic Banding Ligation plus Nadolol and ISMN in the prevention of variceal rebleeding

ISRCTN	ISRCTN26221020
DOI	https://doi.org/10.1186/ISRCTN26221020
Protocol serial number	LEB-VE2002
Sponsor	Individual Sponsor (Spain)
Funder	Health Investigation Fund (Fondo de Investigación Sanitaria), Ministry of Health, PI020739.

Submission date: 28/12/2005
Registration date: 24/03/2006
Last edited: 25/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jaime Bosch
Scientific

Liver Unit
Hospital Clinic
Villarroel 170
Barcelona
08036
Spain

Phone	+34 (0)932275790
Email	jbosch@clinic.ub.es

Study information

Primary study design	Interventional
Study design	Randomized controlled multicenter open study
Secondary study design	Randomised controlled trial
Scientific title	A randomized phase IV clinical trial comparing Nadolol and Isosorbide Mononitrate (ISMN) with the combination of Endoscopic Banding Ligation plus Nadolol and ISMN in the prevention of variceal rebleeding
Study objectives	The combination of endoscopic banding ligation with drug therapy improves the results of drug therapy alone in the prevention of rebleeding in patients with cirrhosis who have suffered an acute variceal bleeding. The assumptions for the sample size were that the control group would have a 32% incidence of rebleeding at one-year, and that this would be reduced to 15% in the experimental group. Since this is a one sided hypothesis, we calculated that with an alpha of 5% and a beta of 20%, at least 160 patients would be required to detect such a difference.
Ethics approval(s)	Date of approval by the ethics committee: 23/Sep/2002. Number: 02-0294.
Health condition(s) or problem(s) studied	Variceal bleeding
Intervention	Control group: nadolol + isosorbide mononitrate for the prevention of rebleeding Experimental group: nadolol + isosorbide mononitrate + endoscopic banding ligation for the prevention of rebleeding.
Intervention type	Other
Primary outcome measure(s)	Rebleeding from any source
Key secondary outcome measure(s)	1. Rebleeding from esophageal varices 2. Rebleeding from other portal hypertensive sources 3. Death 4. Death from variceal bleeding 5. Death from rebleeding 6. Frequency of severe adverse events 7. Relation between changes in hepatic venous pressure gradient and clinical events 8. Development of any complication of portal hypertension or death 9. Changes in variceal size 10. Transfusion requirements 11. Requirement for alternative therapies 12. Costs
Completion date	01/02/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	All
Target sample size at registration	160
Key inclusion criteria	1. Age between 18-75 2. Diagnosis of cirrhosis 3. Hematemesis or melena within 7 days prior to inclusion 4. Esophageal or gastroesophageal varices as the source of bleeding 5. Written informed consent 6. Exclusion of pregnancy in woman of child-bearing potential
Key exclusion criteria	1. Hepatocellular carcinoma >5 cm or multinodular 2.Creatinine >2 mg/dl 3. Child-Pugh ≤13 points 4. Contraindications to beta-adrenergic blockers 5. Contraindications to ISMN 6. Banding ligation in the 3 months before the present episode of variceal bleeding 7. Previous portosystemic derivative therapy 8. Bleeding from fundal or ectopic varices 9. Total portal vein thrombosis or portal vein cavernomatosis 10. The patient was already on beta-adrenergic blockers and ISMN for the prevention of variceal bleeding
Date of first enrolment	01/02/2003
Date of final enrolment	01/02/2005

Locations

Countries of recruitment

Spain

Study participating centre

Liver Unit

Barcelona
08036
Spain

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	pub	01/08/2009		Yes	No

Editorial Notes

25/10/2022: Internal review.