Vonoprazan Efficacy to Prevent Post Variceal Band Ligation Ulcer

Phase 3

Completed

• Conditions: Portal Hypertension; Variceal Hemorrhage; Ulcer Hemorrhage

• Registration Number: NCT05227833
• Lead Sponsor: Alexandria University

Brief Summary

Endoscopic variceal ligation (EVL) is used to control and prevent variceal bleeding in patients with liver cirrhosis, but it can be complicated by bleeding from post-EVL ulcers. the current study aims at evaluating the potential benefit of different acid-suppressive therapies in prevention of post band ligation ulcer/bleeding. We will include 234 patients with cirrhotic portal hypertension undergoing endoscopic band ligation. Patients will be randomly allocated into one group of acid suppressive therapy (Vonoprazan or pantoprazole) versus placebo for 14 days. Re-endoscopy will be done after 2 weeks of treatment to assess the healing of post ligation ulcers. Any form of upper gastrointestinal bleeding will be documented.

Detailed Description

Patients with portal hypertension who have esophageal varices usually are treated by endoscopic band ligation according to the international guidelines to prevent variceal bleeding. After band ligation, patients may suffer from post-ligation ulcer and/or bleeding. In the current study, we evaluate the effectiveness of Vonoprazan, a novel potassium-competitive acid suppressor agent, in prevention of post-ligation ulcer and /or bleeding. We also will compare this drug with the proton-pump inhibitor Pantoprazole and with placebo. We aim to enroll 234 patients who will undergo elective endoscopic variceal ligation according to the BAVINO VII guidelines will be randomly assigned to one of three arms : Vonoprazan 20 mg once daily, Pantoprazole 40 mg once daily, or Placebo (no treatment). The treatment will start from the day of band ligation and will continue for 14 days. After that, a follow up endoscopy will be done to evaluate the site of band ligation. Any ulcer at the ligation site will be documented and its size will be measured. Also, any attack of bleeding from the ulcer site (if present) will be documented. A comparison between the three arms will be done in terms of effectiveness, and bleeding rates.

Safety assessment:

The safety assessment will include all patients who will receive at least 1 dose of their assigned treatment. The safety endpoints will include treatment related adverse effects (TRAEs) grouped by Medical Dictionary for Regulatory Activities version 19.1, system organ class and preferred term, and changes from baseline in an abbreviated physical examination including vital signs, signs of liver cell deterioration, and mean change in laboratory measures including hemogram, liver aminotransferases, serum urea and creatinine, liver function test.

Study Timeline

• Study First Submitted: 2022-01-26
• Study First Submitted QC: 2022-02-03
• Study First Posted: 2022-02-07
• Study Start: 2022-02-15
• Primary Completion: 2022-11-15
• Study Completion: 2022-11-15
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-28
• Last Update Posted: 2024-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 284

Inclusion Criteria

• Patients with liver cirrhosis with portal hypertension who are eligible for endoscopic band ligation (Bleeding varices, or non-bleeder but with risk signs) according to BAVINO VII guidelines
• Patients who completed the study protocol.
• Eligible participants who are willing to comply with the study protocol and provide written consent.

Exclusion Criteria

• Endoscopically confirmed pre-existing esophageal ulcers
• Ongoing therapy with any anti-acid agent,
• Hepatocellular carcinoma
• Portal vein thrombosis
• Previous anti-flux procedure,
• Barrett's esophagus,
• History of liver transplantation,
• Pregnancy, and allergy or past adverse reaction to acid-suppressive therapy
• Estimated glomerular filtration rate < 60 mL/min/1.73 meter square.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Post ligation ulcer : presence (Yes or No), number, and size	At 2 weeks after intervention (EBL)	1. presence of post ligation ulcer (Yes/NO); 2. the number of ulcers if present.; 3. the maximum dimension of an ulcer (if present) in millimeter.
Post endoscopic variceal ligation ulcers	At 2 weeks after intervention	Number of participants who experienced post-ligation ulcer.
Post endoscopic variceal ligation bleeding	during the 2 weeks treatment duration	Number of participants who experienced post-ligation ulcer bleeding.

Secondary Outcome Measures

Name	Time	Method
Number of participants with Vonoprazan-related adverse events as assessed by TRAEs grouped by Medical Dictionary for Regulatory Activities version 19.1	During the 2 weeks of medication use	* The safety assessment will include all patients who will receive at least 1 dose of their assigned treatment.; * The safety endpoints will include treatment related adverse effects (TRAEs) grouped by Medical Dictionary for Regulatory Activities version 19.1, system organ class and preferred term, and changes from baseline in an abbreviated physical examination and laboratory parameters including: * Vital signs,; * New onset hepatic encephalopathy,; * New onset ascites OR Increasing a pre-existing ascites,; * Changes in hemogram,; * Liver aminotransferases,; * Prothrombin time/INR; * Serum Bilirubin; * Serum urea and creatinine.; These data will be collected through: * Recording the baseline clinico-laboratory parameters at the 1st visit; * Re-evaluation of the same parameters at 2 weeks follow-up visit; * Encouraging the patients to communication with the study team in case of any other adverse events that may occur during the treatment duration.