Prevention of Esophageal Variceal Rebleeding

National Science Council, Taiwan

Status and phase: Unknown; Phase 4

Conditions: Esophageal Variceal Rebleeding

Treatments: Drug: pantoloc (proton pump inhibitor); Drug: terlipressin (vasoconstrictor)

Study type: Interventional

Funder types: Other

Identifiers

NCT00863837

NSC

Details and patient eligibility

About

BACKGROUND: Previous studies showed that the combination of endoscopic therapy with vasoconstrictor is better than either vasoconstrictor or endoscopic therapy alone in achieving the successful hemostatsis of acute variceal bleeding. The rationale of using vasoconstrictor is to enhance the efficacy of hemostasis by endoscopic therapy. Nowadays, endoscopic variceal ligation (EVL) has replaced endoscopic injection sclerotherapy (EIS) as the endoscopic treatment of choice in the arresting of acute esophageal variceal hemorrhage. EVL alone can achieve hemotasis up to 97% even in cases of active variceal hemorrhage. However, early rebleeding due to ligation-induced ulcer may be encountered. It appears that prevention of esophageal ulcers and bleeding by a proton pump inhibitor may be more logical than using a vasoconstrictor after cessation of bleeding by EVL.

Thus, the investigators designed a controlled trial to compare the initial hemostasis, early rebleeding rate in cirrhotic patients presenting with acute variceal bleeding receiving either emergency EVL plus vasoconstrictor infusion or losec infusion for 5 days.

Full description

Methods of treatment:

Group 1: Somatostatin 250μg slow bolus IV infusion followed by 250μg per hour (6mg/ 24 hours) or Terlipressin 2mg bolus was instituted on enrollment followed by 1mg per 6 hours for 5 days. The use of either somatostatin or glypressin was at the discretion of doctors in charge. Group 2: Pantoloc 20 mg intravenously per day was instituted on enrollment and continued for 5 days.

Definition of initial hemostasis:

Initial hemostasis was defined as achieving a 24h bleeding-free period within the first 48h after treatment together with stable vital signs based on Baveno consensus criteria.

Very early rebleeding was defined as: UGI bleeding occurred after initial hemostasis and within 5 days after enrollment. UGI bleeding was proven to be from esophageal varices.

Treatment failure is defined as failure to control acute bleeding episodes or very early rebleeding.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. The etiology of portal hypertension is cirrhosis.

2. Age ranges between 18-80 y/o.

3. Patients presenting with acute esophageal variceal bleeding proven by emergency endoscopy within 12 hours. (Acute esophageal variceal bleeding was defined as:

   • when blood was directly seen by endoscopy to issue from an esophageal varix (active bleeding) OR
   • when patients presented with red color signs on their esophageal varices with blood in esophagus or stomach and no other potential site of bleeding identified (inactive bleeding).

4. EVL is performed after confirmation of acute esophageal variceal bleeding. Enrollment time: Immediately after EVL is completed and variceal bleeding is arrested.

Exclusion criteria

1. association with severe systemic illness, such as sepsis, COPD, uremia
2. association with gastric variceal bleeding
3. failure in the control of bleeding by emergency EVL
4. moribund patients, died within 12 hours of enrollment
5. Uncooperative
6. Ever received EIS, EVL within one month prior to index bleeding
7. Child-Pugh's scores > 10

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 2 patient groups, including a placebo group

Arm A

Active Comparator group

Description:

add pantoloc to reduce ulcer bleeding after banding ligation

Treatment:

Drug: pantoloc (proton pump inhibitor)

Arm B: ligation + terlipressin 1mg q6h

Placebo Comparator group

Description:

Arm B, intervention: ligation + terlipressin 1mg q6h

Treatment:

Drug: terlipressin (vasoconstrictor)