Clinical trial NCT05227833: Vonoprazan Efficacy to Prevent Post Variceal Band Ligation Ulcer
Official title: Vonoprazan Vs. Pantoprazole in the Prevention of Post Endoscopic Band Ligation Ulcer/Bleeding in Portal Hypertensive Patients: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Portal Hypertension
Variceal Hemorrhage
Ulcer Hemorrhage
Keywords: Portal Hypertension
Post-ligation ulcer
Vonoprazan
Pantoprazole
Variceal bleeding
Lead sponsor: Alexandria University
Sponsor class: OTHER
Collaborators: name: Alexandria University Hospital, Alexandria, Alexandria Governorate, Egypt
First posted: 2022-02-07
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The enrolled participants after having an endoscopic variceal ligation session will be randomly allocated to one of three interventions (for 14 days):

Vonoprazan 20 mg once before breakfast OR Pantoprazole 40 mg before breakfast OR Placebo (no treatment) at a 1:1 ratio.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Post ligation ulcer : presence (Yes or No), number, and size
timeFrame: At 2 weeks after intervention (EBL)
measure: Post endoscopic variceal ligation ulcers
timeFrame: At 2 weeks after intervention
measure: Post endoscopic variceal ligation bleeding
timeFrame: during the 2 weeks treatment duration
Secondary outcomes:
measure: Number of participants with Vonoprazan-related adverse events as assessed by TRAEs grouped by Medical Dictionary for Regulatory Activities version 19.1
timeFrame: During the 2 weeks of medication use
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Alexandria Main University Hospital
Study officials:
affiliation: University of Alexandria
name: Sameh Lashen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.