Pantoprazole After Prophylactic Endoscopic Variceal Treatment

Pantoprazole After Prophylactic Endoscopic Variceal Treatment in Cirrhosis (PPEC): Protocol of a Multicenter Randomized Controlled Trial

Traditionally, it is considered that gastric acid delays ulcer healing, and acid suppression can reduce the risk of post-banding ulcer bleeding and promote mucosal healing at the ulcer site. A systematic review and meta-analysis performed by our team demonstrated that acid suppression significantly reduced the incidence of gastrointestinal bleeding (GIB) following prophylactic endoscopic variceal ligation (EVL), but had no significant effect on the incidence of mortality, adverse events, or length of stay. Similarly, another systematic review and meta-analysis performed by Lin et al. indicated that proton pump inhibitor (PPI) significantly reduced the incidence of GIB after therapeutic or prophylactic endoscopic variceal treatment (EVT), and the efficacy of PPI in reducing post-EVT GIB is related to the duration of PPI. However, previous studies have indicated that long-term use of PPI may increase the risk of bacterial infections and hepatic encephalopathy in patients with cirrhosis. Therefore, current guidelines suggest that PPI should be discontinued after EVT, unless the patient has a clear indication for PPI. However, the quality of evidence is poor due to the small sample sizes, predominantly retrospective designs, and inconsistencies in follow-up duration of previous studies. In current clinical practice, most physicians still prefer to use PPI routinely after EVT to prevent post-EVT GIB. Given the ongoing controversy regarding the routine use of PPI after EVT, we plan to conduct a multicenter randomized controlled trial to to explore the effect of PPI after prophylactic EVT on the incidence of short-term GIB, adverse events, and mortality in patients with cirrhosis and esophagogastric varices (EGV).

Study Overview

• Status: Enrolling by invitation
• Conditions: Liver Cirrhosis; Esophageal and Gastric Varices
• Intervention / Treatment: Drug: Pantoprazole

Detailed Description

Overall, 208 patients with cirrhosis and EGV undergoing prophylactic EVT will be enrolled. They will be randomly assigned at a ratio of 1:1 to the pantoprazole group and the control group. The primary endpoint is 6-week GIB. The secondary endpoints include: (1) 6-week all-cause death; (2) hierarchical composite endpoint of all-cause death or 6-week GIB. The safety outcome is 6-week adverse events, which contains complications potentially related to EVT or PPI within 6 weeks after EVT.

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110840
      • Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. patients who are diagnosed with liver cirrhosis by liver biopsy and/or a combination of clinical manifestation, laboratory tests, and imaging examinations;
2. patients who are diagnosed with esophageal varix (EV) or gastroesophageal varix 1 (GOV1) by endoscopy;
3. patients who undergo EVT for EV and/or gastric varices;
4. patients who undergo EVT for either primary or secondary prophylaxis of EVB;
5. patients aged ≥18 years, regardless of gender;
6. patients who sign their informed consent forms.

Exclusion Criteria:

1. patients with a diagnosis of acute variceal bleeding before enrollment;
2. patients with definite indications for PPI (reflux esophagitis, peptic ulcer, Zollinger-Ellison syndrome, etc.) at admission;
3. patients with definite indications for PPI (reflux esophagitis, peptic ulcer, etc.) discovered during EVT;
4. patients who are allergic to PPI or had intolerable adverse reactions to PPI previously;
5. patients with severe cardiovascular diseases, cerebrovascular diseases, or renal impairment;
6. patients with severe hematological disorders;
7. patients who were pregnant, lactating, or preparing for pregnancy;
8. patients who have already participated in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group
Experimental: pantoprazole group	Drug: Pantoprazole; Participants assigned to the pantoprazole group should receive intravenous pantoprazole 40 mg once daily immediately after EVT for a duration of 1 to 7 days until discharge, followed by oral pantoprazole 40 mg once daily until the total duration is 2 weeks. Patients assigned to the control group should not receive any acid suppression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of 6-week GIB	binary outcome	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of 6-week all-cause death	time-to-event outcome	6 weeks
Proportion of 6-week adverse events	Proportion of 6-week adverse events (binary outcome) is also the safety outcome, which is defined as complications potentially related to EVT or PPI within 6 weeks after EVT. The complications related to PPI primarily include: (1) clostridium difficile infection; (2) pneumonia; (3) hepatic encephalopathy; (4) spontaneous bacterial peritonitis; and (5) other adverse events. Except for GIB, the complications related to EVT primarily include: (1) retrosternal pain/discomfort; (2) nausea/vomiting; (3) heartburn/acid regurgitation; (4) fever; (5) diarrhea; (6) abdominal pain; and (7) other adverse events.	6 weeks
hierarchical composite endpoint of all-cause death or 6-week GIB	The hierarchy of the composite endpoint is death due to all cause (time-to-event) and then 6-week GIB (binary).	6 weeks

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region
• Investigators: Study Director: Xingshun Qi, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)

Publications and helpful links

General Publications

• 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.
• Zhang YY, Wang L, Shao XD, Zhang YG, Ma SZ, Peng MY, Xu SX, Yin Y, Guo XZ, Qi XS. Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization. World J Gastrointest Surg. 2023 Jan 27;15(1):82-93. doi: 10.4240/wjgs.v15.i1.82.
• Zhu J, Qi X, Yu H, Su C, Guo X. Acid suppression in patients treated with endoscopic therapy for the management of gastroesophageal varices: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2018 Jun;12(6):617-624. doi: 10.1080/17474124.2018.1456918. Epub 2018 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: adverse events; proton pump inhibitor; liver cirrhosis; endoscopic therapy; esophageal and gastric varices
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Fibrosis; Hypertension, Portal; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis; Esophageal and Gastric Varices; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pantoprazole
• Other Study ID Numbers: XHNKKY-PPEC

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