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

Esophageal and Gastric Varices Clinical Trial

Official title:

Carvedilol Plus Endoscopic Cyanoacrylate Injection Versus Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02504723
• Other study ID #: VGHKS11-CT10-11
• Status: Recruiting
• Phase: Phase 4
• First received: July 18, 2015
• Last updated: October 29, 2016
• Start date: January 2011
• Est. completion date: November 2016

Study information

• Verified date: October 2016
• Source: Kaohsiung Veterans General Hospital.
• Contact: Wen-Chi Chen, MD
• Phone: +886-7-3422121
• Email: wcchen[@]vghks.gov.tw
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal and Gastric Varices

Intervention

Drug:
• carvedilol
Oral carvedilol is started after randomization at an initial dose of 6.25 mg daily. Doses are increased every 3 days during the admission or every 7 days in the out-patient clinics until the maximum tolerated dose, aiming at reducing resting pulse rate by 25 percent but not below 55 beats per minute with systolic blood pressure >90 mm Hg.
• cyanoacrylate
The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.

Locations

Country	Name	City	State
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Kaohsiung Veterans General Hospital.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rebleeding from gastric varices confirmed by endoscopy		Within 5 years	No
Secondary	All complications		Within 5 years	Yes
Secondary	All cause mortality		Within 5 years	No