Proton Pump Inhibitor Plus Propranolol Versus Proton Pump Inhibitor Alone on Peptic Ulcer Healing in Patients With Liver Cirrhosis (PU)

Proton Pump Inhibitor Plus Propranolol Versus Proton Pump Inhibitor Alone on Peptic Ulcer Healing in Patients With Liver Cirrhosis: a Randomized Trail

Proton pump inhibitor plus propranolol versus proton pump inhibitor alone on peptic ulcer healing in patients with liver cirrhosis: a randomized trail

Study Overview

• Status: Terminated
• Conditions: Liver Cirrhosis; Peptic Ulcer
• Intervention / Treatment: Drug: Proton-pump inhibitor; Drug: Propranolol+Proton-pump inhibitor

Detailed Description

Portal hypertension is responsible for the development of portosystemic collaterals. The hemodynamic alternations may result in mucosal and vascular changes along gastrointestinal (GI) tract as well. According to several epidemiological studies, cirrhotic patients are at a higher risk of developing peptic ulcers, delayed healing, and a higher frequency of ulcer recurrence. The death rate from peptic ulcer disease in cirrhotic patients has been reported to be five times higher than that of the general population. The exact mechanism remains incompletely understood, but may be related to impaired mucosal defense mechanisms. Aggressive factors such as Helicobacter pylori and gastric acid may not be the predominant etiology in such circumstances. Sarfeh et al. found gastric mucosa of portal hypertensive rats, compared with that of controls, has distinctive functional and histologic abnormalities that can explain its increased susceptibility to erosive injury. Auroux et al. found gastroduodenal ulcer was independently associated only with the severity of the hypertensive gastropathy in cirrhotics. Chen et al. found portal hypertension with a hepatic venous pressure gradient > 12 mmHg may be an important factor contributing to the increased prevalence of gastric ulcer observed in patients with liver cirrhosis. Thereby, we presumed that clinically significant portal hypertension may play a role in development of peptic ulcer in cirrhotic patients. Lebrec et al. elucidated non-selective beta-blocker (NSBB) could significantly decrease portal pressure and lower the risk of GI bleeding in patients with cirrhosis. Kitano et al. found portal hypotensive treatment with NSBB, reduces ethanol-induced gastric mucosal damage in portal hypertensive rats and improves endoscopic signs of portal hypertensive gastropathy in cirrhosis patients. We designed a 2-year randomized trial to evaluate the effectiveness of proton pump inhibitor with or without propranolol on ulcer healing and the incidence of ulcer bleeding in patients with cirrhosis and peptic ulcers.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 20 and 85 years old
• Liver cirrhosis associated with esophageal varices or gastric varices
• Gastric ulcer or duodenal ulcer ,size bigger or egual than 0.5 cm

Exclusion Criteria:

• Acute bleeding
• Steroid or NSAID user
• Pregnancy, or the patients with other terminal illness (such as other terminal cancers, heart failure, renal failure...)
• Propranolol contraindications (such as atrioventricular block, heart failure, chronic obstructive pulmonary disease, asthma, poorly controlled diabetes, severe peripheral arterial disease...)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Proton-pump inhibitor; PPI: Pariet EC 20 mg/QDAC	Drug: Proton-pump inhibitor; PPI: Pariet EC 20mg/QDAC; Other Names: PPI; Pariet EC
Active Comparator: Propranolol+Proton-pump inhibitor; Propranolol: Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate>55 or systemic blood pressure>90mmHg) PPI: Pariet EC 20 mg/QDAC	Drug: Propranolol+Proton-pump inhibitor; Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate>55 or systemic blood pressure >90mmHg) PPI: Pariet EC 20mg/QDAC; Other Names: Inderal; Cardolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healing of peptic ulcer	if propranolol can help cure peptic ulcer	2 months
Bleeding rate of peptic ulcer	if propranolol can help decrease the rate of ulcer bleeding	2 months

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan
• Investigators: Principal Investigator: Ming-Chih mchou@vghtpe.gov.tw, MD, Institutional Review Board, Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2016
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 19, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Portal hypertension; Peptic ulcer; Non-selective beta-blocker; Proton pump inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Liver Diseases; Intestinal Diseases; Duodenal Diseases; Fibrosis; Ulcer; Liver Cirrhosis; Peptic Ulcer; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Propranolol; Proton Pump Inhibitors
• Other Study ID Numbers: V106C-137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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