Clinical trial NCT02740166: Preventing Recurrent Bleeding After Eradication of Esophageal Varices
Official title: Banding Ligation Plus Propranolol Versus Banding Ligation to Prevent Rebleeding of Esophageal Varices
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Esophageal Varices
Keywords: Esophageal Varices; propranolol; banding ligation
Lead sponsor: Kaohsiung Veterans General Hospital.
Sponsor class: OTHER
First posted: 2016-04-15
Enrollment: 212
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Esophageal variceal bleeding is a severe complication of portal hypertension. Banding ligation plus non-selective beta-blockers is the current recommendation for prevention of recurrent bleeding. However, the optimal duration of use of non-selective beta-blockers is not well defined. This study aims at comparing the rebleeding rate and adverse effects in patients using or without using propranolol after eradication of esophageal varices.

Detailed description: Cirrhotic patients with acute or recent esophageal variceal bleeding undergo banding ligation at 1-month interval until eradication of esophageal varices. Patients start propranolol (start with 30 mg daily) at 6th day after control of acute bleeding till eradication of esophageal varices, aiming at decreasing pulse rate to 25% or to 55 bpm while systolic pressure is above 85 mmHg. Patients randomized to propranolol group continue propranolol after eradication of esophageal varices. Patients randomized to banding ligation group discontinue propranolol after eradication of esophageal varices. Patients are followed to evaluate the incidence of rebleeding, adverse effects and survival.

Eligibility criteria: Inclusion Criteria:

* Age of 20 to 80 years
* Cirrhotic patients with acute or recent esophageal variceal bleeding proven by an endoscopy
* Stable hemodynamic condition for at least 3 days after banding ligation

Exclusion Criteria:

* Hepatocellular carcinoma or other malignancy
* Stroke or active sepsis
* Chronic kidney disease under renal replacement therapy
* Contraindications to non-selective beta-blockers
* A history of non-selective beta-blockers use, sclerotherapy, banding ligation, transjugular intrahepatic porto-systemic shunt, or shunt surgery
* Serum total bilirubin \>10 mg/dL
* Grade III/IV hepatic encephalopathy
* Refractory ascites
* Hepato-renal syndrome
* Pregnancy
* Severe heart failure (NYHA Fc III/IV)
* Bronchial asthma or chronic obstructive pulmonary disease
* Second or third degree atrioventricular block
* Sick sinus syndrome
* Pacemaker use
* Severe hypotension
* Refusal to participate

Primary outcomes:
measure: recurrent esophageal variceal bleeding
timeFrame: 6 years
measure: mortality or liver transplantation
timeFrame: 6 years
Secondary outcomes:
measure: adverse effects
timeFrame: 6 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
Study officials:
affiliation: Kaohsiung Veterans General Hospital.
name: Wen-Chi Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gonzalez R, Zamora J, Gomez-Camarero J, Molinero LM, Banares R, Albillos A. Meta-analysis: Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis. Ann Intern Med. 2008 Jul 15;149(2):109-22. doi: 10.7326/0003-4819-149-2-200807150-00007.
citation: Lo GH, Lai KH, Cheng JS, Chen MH, Huang HC, Hsu PI, Lin CK. Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective, randomized trial. Hepatology. 2000 Sep;32(3):461-5. doi: 10.1053/jhep.2000.16236.
citation: de la Pena J, Brullet E, Sanchez-Hernandez E, Rivero M, Vergara M, Martin-Lorente JL, Garcia Suarez C. Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial. Hepatology. 2005 Mar;41(3):572-8. doi: 10.1002/hep.20584.
citation: Kumar A, Jha SK, Sharma P, Dubey S, Tyagi P, Sharma BC, Sarin SK. Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence. Gastroenterology. 2009 Sep;137(3):892-901, 901.e1. doi: 10.1053/j.gastro.2009.05.049. Epub 2009 May 27.