PPIs and In-Hospital Morbidity in Acute Variceal Bleeding With Chronic Liver Disease (Liver-IMPACT)

In-Hospital Morbidity Associated With Proton Pump Inhibitors in Acute Variceal Bleeding and Chronic Liver Disease Treatment

With this study, the investigators pretend to describe intrahospital morbidity in patients living with cirrhosis (PLC) who present to the emergency department with variceal bleeding (VB).

This study is a longitudinal, prospective, experimental, analytical single-center clinical trial. The study will be performed in the Hospital Universitario "Jose E. González" de la Factultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.

The studied population consists of adult-age patients with previous, recent, or new diagnoses of cirrhosis who present to the ED with VH without shock, infection, or acute or chronic disease with a <30% probability of death (CLIF-C <50). The exclusion criteria involve minor age, Acute Liver Failure (ALF), ICU patients, Hepatorenal Syndrome, sepsis or infection, and shock on admission except for hypovolemic and CLIF-C >50 points. Elimination criteria involve patients who want to discontinue treatment and patients with confounding endoscopic findings (Erosive esophagitis, peptic ulcers, duodenal ulcers, bleeding GAVE, and atrophic gastritis).

After the endoscopic intervention, the investigators will propose inclusion. After acceptance with Informed Consent, the investigators will randomize the patients to receive or not receive Omeprazole/ Pantoprazole 40 mg IV per day until discharge. The primary outcome will represent several morbidity situations in these patients, including Hepatic Encephalopathy grades III and IV, intra-hospital infections, re-bleeding, shock, and acute kidney failure.

The secondary outcomes include the individual analysis of each component of our compound primary outcome, mortality by day 30, differences when grouping patients by Child-Pugh stratification, and comparing results in patients receiving omeprazole for more or less than 5 days.

Study Overview

• Status: Recruiting
• Conditions: Morbidity
• Intervention / Treatment: Drug: Omeprazole/ Pantoprazole 40 mg IV

Detailed Description

This is a prospective, randomized, and blinded study designed to assess the impact of proton pump inhibitor (PPI) use on in-hospital morbidity during acute variceal bleeding in patients with chronic liver disease. The clinical rationale emerges from ongoing debate regarding the safety and utility of acid suppression therapy in this population, particularly during hospitalization for portal hypertension-related bleeding.

Following initial stabilization and confirmation of upper gastrointestinal bleeding, patients undergo diagnostic endoscopy. Upon identification of varices or portal hypertensive gastropathy, eligible individuals are randomized to either continue omeprazole/ pantoprazole (40 mg daily) or discontinue PPI therapy. Randomization is conducted using computer software, and allocation concealment is maintained from the principal investigator.

Standard care protocols-including administration of vasoactive agents, prophylactic antibiotics, and endoscopic therapy-remain unaltered. The only experimental intervention involves PPI exposure during hospitalization. Clinical, biochemical, and radiological data are collected systematically throughout the hospital stay. In patients presenting with ascites, diagnostic paracentesis is performed as indicated. Events including infection, renal dysfunction, rebleeding, encephalopathy, and circulatory failure are monitored until discharge.

This study is being conducted at a tertiary university hospital with advanced endoscopy and critical care infrastructure. Institutional review board approval has been obtained. Written informed consent is obtained from each participant or their legal representative prior to enrollment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Luis A González Torres, MD; Phone Number: +5218116091332; Email: Luis37torres@gmail.com

Study Locations

• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Recruiting
      • Hospital Universitario "Jose E. González" de la Facultad de Medicina, Universidad Autónoma de Nuevo León

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Adult
• Cirrhosis
• Variceal Bleeding with only endoscopic findings consistent with portal hypertension complications
• Hypovolemic shock and Variceal bleeding

Exclusion Criteria:

• Shock of any type other than hypovolemic.
• No cirrhotic patients
• Patients that have severe Hepatic Encephalopathy at admission (West Haven 3 and 4)
• Hepatorenal syndrome
• Acute on chronic with CLIF-C >50 points
• Septic patients
• Spontaneous Bacterial Peritonitis

Elimination Criteria

• Voluntary removal of the study
• Violation of the study protocol
• Patients in the no PBI group that need prolonged mecánica ventilación.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omeprazole or Pantoprazole 40 mg IV per day; These patients are to receive omeprazole after randomization.	Drug: Omeprazole/ Pantoprazole 40 mg IV; Daily until discharge
No Intervention: No Proton Bomb Inhibitor; These patients are not to receive omeprazol after randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity	The primary outcome is a composite dichotomous outcome represented by morbidity situations, including Hepatic Encephalopathy, intra-hospital infections, re-bleeding, shock, and acute kidney failure.	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocurrence of Hepatic Encefalopathy	Binary outcome yes/ no	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
Ocurrence of Acute Kidney Injury	Acute Kidney Failure binary yes/no	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
Ocurrence of Shock	All types of shock except hypovolemic	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
Ocurrence of Re-bleeding	Re-bleeding after endoscopic intervention	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
Ocurrence of any kind of Infection	Infections after randomization	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
In-Hospital Mortality	The investigators will assess Mortality during hospitalization	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
Omeprazol <or>5 days morbidity	Patients who received more than or less than 5 days of omeprazole during hospitalization and morbidity	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
30 day Mortality	The investigators will assess mortality by day 30, independently of admission status.	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
60 day Mortality	The investigators will assess mortality by day 60, independently of admission status.	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.
90 day Mortality	The investigators will assess mortality by day 60, independently of admission status.	From the date of randomization until hospital discharge or death, assessed up to 13 weeks.

Collaborators and Investigators

• Sponsor: Universidad Autonoma de Nuevo Leon

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): September 20, 2026

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Morbidity; Variceal Bleeding; Proton Bomb Inhibitors
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Hemorrhage; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pantoprazole; Omeprazole
• Other Study ID Numbers: GA24-00007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The investigators will decide after the finishing of this work

Drug and device information, study documents

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