Esophageal and Gastric Varices
Conditions
Keywords
Gastric varices, cyanoacrylate, carvedilol
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.
Interventions
DRUGcarvedilol
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.
DRUGcyanoacrylate
The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.
Sponsors
Kaohsiung Veterans General Hospital.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rebleeding From Gastric Varices | Within 6 years | Rebleeding from gastric varices during the follow-up period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cause Mortality or Liver Transplantation | Within 6 years | All cause mortality or liver transplantation during the study period |
| All Adverse Effects | Within 6 years | All adverse effects during the study period |
| All Upper Gastrointestinal Bleeding | Within 6 years | All upper gastrointestinal bleeding during the follow-up period |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
cyanoacrylate: The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. | 60 |
| Cyanoacrylate Injection The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.
cyanoacrylate: The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. | 61 |
| Total | 121 |
Baseline characteristics
| Characteristic | Cyanoacrylate Injection Plus Carvedilol | Cyanoacrylate Injection | Total |
|---|---|---|---|
| Age, Continuous | 56.52 years STANDARD_DEVIATION 10.87 | 56.26 years STANDARD_DEVIATION 12.08 | 56.39 years STANDARD_DEVIATION 11.45 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 39 Participants |
| Sex: Female, Male Male | 41 Participants | 41 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 60 | 19 / 61 |
| other Total, other adverse events | 32 / 60 | 9 / 61 |
| serious Total, serious adverse events | 0 / 60 | 0 / 61 |
Outcome results
Primary
Rebleeding From Gastric Varices
Rebleeding from gastric varices during the follow-up period
Time frame: Within 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cyanoacrylate Injection Plus Carvedilol | Rebleeding From Gastric Varices | 14 Participants |
| Cyanoacrylate Injection | Rebleeding From Gastric Varices | 21 Participants |
Secondary
All Adverse Effects
All adverse effects during the study period
Time frame: Within 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cyanoacrylate Injection Plus Carvedilol | All Adverse Effects | 32 Participants |
| Cyanoacrylate Injection | All Adverse Effects | 9 Participants |
Secondary
All Cause Mortality or Liver Transplantation
All cause mortality or liver transplantation during the study period
Time frame: Within 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cyanoacrylate Injection Plus Carvedilol | All Cause Mortality or Liver Transplantation | 13 Participants |
| Cyanoacrylate Injection | All Cause Mortality or Liver Transplantation | 20 Participants |
Secondary
All Upper Gastrointestinal Bleeding
All upper gastrointestinal bleeding during the follow-up period
Time frame: Within 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cyanoacrylate Injection Plus Carvedilol | All Upper Gastrointestinal Bleeding | 17 Participants |
| Cyanoacrylate Injection | All Upper Gastrointestinal Bleeding | 29 Participants |