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

Official title

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

Overview

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.

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.

Interventions

• Drug Omeprazole 40 mg IV
  Daily until discharge
• Drug pantoprazole 40 mg iv
  Daily until discharge if omeprazole is unavailable.

Primary outcome measures

• Morbidity [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]

Secondary outcome measures (10)

• Ocurrence of Hepatic Encefalopathy [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• Ocurrence of Acute Kidney Injury [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• Ocurrence of Shock [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• Ocurrence of Re-bleeding [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• Ocurrence of any kind of Infection [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• In-Hospital Mortality [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• Omeprazol <or>5 days morbidity [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• 30 day Mortality [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• 60 day Mortality [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]
• 90 day Mortality [Time frame: From the date of randomization until hospital discharge or death, assessed up to 13 weeks.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Mexico · 1 center

• Hospital Universitario "Jose E. González" de la Facultad de Medicina, Universidad Autónoma — Monterrey

Identifiers

NCT: NCT06861478 · GA24-00007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗