Carvedilol as an Adjunct to Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding

Phase 4

Completed

Conditions: Esophageal and Gastric Varices

Interventions: Drug: carvedilol
Drug: cyanoacrylate

Registration Number: NCT02504723

Lead Sponsor: Kaohsiung Veterans General Hospital.

Brief Summary: Gastric variceal obturation is the current endoscopic therapy of choice for gastric variceal bleeding but is associated with a high rebleeding rate. Carvedilol is a potent non-selective β-blocker. The role of carvedilol in the prevention of recurrent gastric variceal bleeding is not studied. This study aimed at evaluating the efficacy of carvedilol as an adjunct to gastric variceal obturation in the secondary prophylaxis of gastric variceal bleeding.

Detailed Description: Gastric variceal bleeding is a lethal complication of portal hypertension. The rebleeding rate ranged between 30% to 50% in patients after initial hemostasis. Endoscopic cyanoacrylate injection is currently the choice of endoscopic therapy of acute gastric variceal bleeding and prevention of recurrent bleeding. However, the rebleeding rate is still high in the patients undergoing repeated endoscopic cyanoacrylate injection.

Non-selective β-blockers are frequently used for the secondary prophylaxis of variceal bleeding. In the case of esophageal varices, combination of non-selective β-blockers and endoscopic therapy significantly lowers the rebleeding rate compared with endoscopic therapy alone. However, propranolol failed to decrease the rebleeding rate as an adjunct to endoscopic cyanoacrylate injection and was associated with a higher incidence of adverse effects in gastric variceal bleeding patients. A more potent non-selective β-blocker than propranolol might further decrease portal pressure and decrease the rebleeding rate.

Carvedilol is a potent non-selective β-blocker with both beta and alpha-1 blocker effect. It significantly lowers portal pressure even in propranolol non-responders. However, it is unclear weather carvedilol will play a role in the prevention of recurrent gastric variceal bleeding. The investigators conducted a randomized controlled trial to compare the efficacy of carvedilol combined with endoscopic cyanoacrylate injection with endoscopic cyanoacrylate injection alone in secondary prophylaxis of gastric variceal bleeding.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 121

Inclusion Criteria

Age of 20 to 80 years
Cirrhotic patients with acute gastric variceal bleeding proven by an endoscopy within 24 h of bleeding
Stable hemodynamic condition for at least 3 days after cyanoacrylate injection

Exclusion Criteria

Previous treatment of gastric varices, including endoscopic therapy, transjugular intrahepatic porto-systemic shunt, or surgery
Contraindications to non-selective beta-blockers or cyanoacrylate injection
Serum total bilirubin >10 mg/dL
Grade III/IV hepatic encephalopathy
Hepato-renal syndrome
Severe heart failure (NYHA Fc III/IV)
Chronic kidney disease under renal replacement therapy
Refractory ascites
Malignancy other than hepatocellular carcinoma
Pregnancy
Pacemaker use
Refusal to participate

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyanoacrylate injection plus carvedilol	cyanoacrylate	The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. Oral carvedilol is administrated during the whole study period, starting at 6.25 mg daily and increased until the maximum tolerated dose.
Cyanoacrylate injection	cyanoacrylate	The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.
Cyanoacrylate injection plus carvedilol	carvedilol	The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. Oral carvedilol is administrated during the whole study period, starting at 6.25 mg daily and increased until the maximum tolerated dose.

Primary Outcome Measures

Name	Time	Method
Rebleeding From Gastric Varices	Within 6 years	Rebleeding from gastric varices during the follow-up period

Secondary Outcome Measures

Name	Time	Method
All Cause Mortality or Liver Transplantation	Within 6 years	All cause mortality or liver transplantation during the study period
All Upper Gastrointestinal Bleeding	Within 6 years	All upper gastrointestinal bleeding during the follow-up period
All Adverse Effects	Within 6 years	All adverse effects during the study period