Vonoprazan Efficacy to Prevent Post Variceal Band Ligation Ulcer

Vonoprazan Vs. Pantoprazole in the Prevention of Post Endoscopic Band Ligation Ulcer/Bleeding in Portal Hypertensive Patients: a Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Portal Hypertension; Variceal Hemorrhage; Ulcer Hemorrhage
• Intervention / Treatment: Drug: Vonoprazan fumarate (Vonaspire); Drug: Pantoprazole 40mg; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 284
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21521
    • Alexandria main university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vonoprazan; Vonoprazan (vonaspire 20 mg), tablets, one tablet per day before breakfast for 14 days starting from the day of band ligation.	Drug: Vonoprazan fumarate (Vonaspire); Patients assigned to Vonoprazan (vonaspire) tablets will receive a daily dose of 20 mg before breakfast starting from the first day of band ligation.; Other Names: Vonoprazan
Active Comparator: Pantoprazole; Pantoprazole (Controloc 40 mg OR Antopral 40 mg OR Perloc 40 mg), tablets, one tablet per day before breakfast for 14 days, starting from the day of band ligation.	Drug: Pantoprazole 40mg; Patients assigned to Pantoprazole tablets (Controloc OR Antopral OR Perloc) will receive a daily dose of 40 mg before breakfast starting from the first day of band ligation.; Other Names: Pantoprazole Sodium
Placebo Comparator: Placebo; No acid suppressive medications will be described.	Other: Placebo; No Intervention

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Vonoprazan-related adverse events as assessed by TRAEs grouped by Medical Dictionary for Regulatory Activities version 19.1	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/INRSerum BilirubinSerum 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.	During the 2 weeks of medication use

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: Sameh Lashen, MD, University of Alexandria

Publications and helpful links

General Publications

• Kang SH, Yim HJ, Kim SY, Suh SJ, Hyun JJ, Jung SW, Jung YK, Koo JS, Lee SW. Proton Pump Inhibitor Therapy Is Associated With Reduction of Early Bleeding Risk After Prophylactic Endoscopic Variceal Band Ligation: A Retrospective Cohort Study. Medicine (Baltimore). 2016 Feb;95(8):e2903. doi: 10.1097/MD.0000000000002903.
• Lin L, Cui B, Deng Y, Jiang X, Liu W, Sun C. The Efficacy of Proton Pump Inhibitor in Cirrhotics with Variceal Bleeding: A Systemic Review and Meta-Analysis. Digestion. 2021;102(2):117-127. doi: 10.1159/000505059. Epub 2020 Feb 21.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): August 30, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Pantoprazole; Variceal bleeding; Vonoprazan; Portal Hypertension; Post-ligation ulcer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Hypertension; Ulcer; Hemorrhage; Hypertension, Portal; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: 0305413

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No