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

• ClinicalTrials.gov Identifier: NCT02504723
• Recruitment Status: Completed
• First Posted: July 22, 2015
• Results First Posted: July 27, 2017
• Last Update Posted: August 21, 2017
• Sponsor: Kaohsiung Veterans General Hospital.
• Information provided by (Responsible Party): Wen-Chi Chen, Kaohsiung Veterans General Hospital.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Esophageal and Gastric Varices	Drug: carvedilol; Drug: cyanoacrylate	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Carvedilol Plus Endoscopic Cyanoacrylate Injection Versus Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding
• Actual Study Start Date: December 2011
• Actual Primary Completion Date: February 2017
• Actual Study Completion Date: February 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cyanoacrylate injection plus 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.	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 was achieved or up to 25 mg daily, aiming at reducing resting pulse rate by 25 percent but not below 55 beats per minute with systolic blood pressure >90 mm Hg.; Drug: cyanoacrylate; The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.
Active Comparator: Cyanoacrylate injection; The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.	Drug: cyanoacrylate; The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.

Outcome Measures

Primary Outcome Measures :

1. Rebleeding From Gastric Varices [ Time Frame: Within 6 years ]
   Rebleeding from gastric varices during the follow-up period

Secondary Outcome Measures :

1. All Upper Gastrointestinal Bleeding [ Time Frame: Within 6 years ]
   All upper gastrointestinal bleeding during the follow-up period
2. All Cause Mortality or Liver Transplantation [ Time Frame: Within 6 years ]
   All cause mortality or liver transplantation during the study period
3. All Adverse Effects [ Time Frame: Within 6 years ]
   All adverse effects during the study period

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Taiwan

Kaohsiung Veterans General Hospital

Kaohsiung, Taiwan, 813

Sponsors and Collaborators

Kaohsiung Veterans General Hospital.

Investigators

• Principal Investigator: Wen-Chi Chen, MD; Kaohsiung Veterans General Hospital.

  Study Documents (Full-Text)

Documents provided by Wen-Chi Chen, Kaohsiung Veterans General Hospital.:

Study Protocol and Statistical Analysis Plan  [PDF] December 12, 2011

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chen WC, Hsin IF, Chen PH, Hsu PI, Wang YP, Cheng JS, Lin HS, Hou MC, Lee FY. Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2356-2363.e2. doi: 10.1016/j.cgh.2019.02.021. Epub 2019 Feb 14.

• Responsible Party: Wen-Chi Chen, MD, Kaohsiung Veterans General Hospital.
• ClinicalTrials.gov Identifier: NCT02504723
• Other Study ID Numbers: VGHKS11-CT10-11
• First Posted: July 22, 2015
• Results First Posted: July 27, 2017
• Last Update Posted: August 21, 2017
• Last Verified: July 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wen-Chi Chen, Kaohsiung Veterans General Hospital.:

Gastric varices; cyanoacrylate; carvedilol

Additional relevant MeSH terms:

Esophageal and Gastric Varices; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Hypertension, Portal; Liver Diseases; Carvedilol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antihypertensive Agents; Antioxidants; Protective Agents; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasodilator Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists