Ilaprazole for the Treatment and Prevention of Peptic Ulcer Bleeding in Chinese Patients

Efficacy and Safety of Intravenous IIaprazole for Peptic Ulcer Bleeding: A Randomized, Double-Blind, Omeprazole-Controlled, Multicenter, and Phase 3 Trail in China

The purpose of this phase study is to confirm the efficacy and safety by compare ilaprazole and omeprazole in the treatment and prevention of peptic ulcer bleeding. Patients with endoscopically diagnosed peptic ulcer bleeding were enrolled in a multi-center, stratified randomized, non-inferiority test, double-blind, parallel and positive-controlled trial. They were randomly assigned into two groups, ilaprazole and omeprazole, to be treated for up to 30 days. The primary endpoint was the hemostasis rate at the end of 72 hours. Secondary end points include ulcer staging changes within 72 hours, effective rate of hemostasis, hemostasis duration, average blood transfusion and rebleeding rate, etc.

Study Overview

• Status: Completed
• Conditions: Peptic Ulcer Hemorrhage
• Intervention / Treatment: Drug: Ilaprazole; Drug: Ilaprazole tablet; Drug: amoxicillin and clarithromycin; Drug: Omeprazole

Detailed Description

Patients with endoscopically diagnosed gastric and duodenal ulcer bleeding were randomly assigned into two groups, ilaprazole and omeprazole. 360 patients were administrated 10 mg ilaprazole daily (at day 1-3) through intravenous infusion within 30min with first dose doubling. Other 180 patients were administrated 40 mg omeprazole twice daily (at day 1-3) through intravenous infusion for 30min. Since 4th day, both group taken oral ilaprazole tablets 10mg each day till 30th day; And the Patients who with helicobacter pylori infection were provided amoxicillin and clarithromycin as complimentary therapy for two weeks. The efficacy of ilaprazole and omeprazole was evaluated by the primary endpointthe-hemostasis rate at the end of 72 hours in the total population, high-risk groups and low-risk groups and secondary end points including ulcer staging changes within 72 hours, effective rate of hemostasis, hemostasis duration, average blood transfusion, the need to switch to other treatments (endoscopic treatment or surgery, etc.), the disappearance time of ulcer pain and rebleeding rate. This phase Ⅲ clinical trial was designed to confirm the efficacy and safety of ilaprazole in the treatment of peptic ulcer bleeding and to pride a basis for registration.

• Study Type: Interventional
• Enrollment (Actual): 540
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. were 18-70 years of age, male or female.
2. had symptoms of hematemesis, hematochezia, melena within 24 hours and clinically diagnosed as peptic ulcer bleeding.
3. had endoscopically diagnosed gastric or duodenal ulcer bleeding and 3mm ≤ ulcer diameter ≤ 15mm.
4. underwent local hemostasis according to "Acute non-variceal upper gastrointestinal bleeding guidelines (2009, Hangzhou)" Forrest grading; multiple ulcers was judged by the higher level.
5. voluntarily sign informed consent

Exclusion Criteria:

1. had hemorrhagic shock ( systolic blood pressure<90mmHg) or require surgery.
2. were non-ulcer bleeding and gastric ulcer biopsy proved malignant.
3. had gastrectomy and gastrointestinal anastomosis.
4. were suffering from serious heart, liver, brain, lung, kidney and other serious diseases.
5. had coagulation disorders (laboratory tests showed that platelets <80 × 109 / L, PT abnormal and exceed the normal control for 3 seconds, APTT than the normal control for 10 seconds).
6. had hypersensitivity or idiosyncratic reaction to ilaprazole, omeprazole, esomeprazole or any other benzimidazole.
7. had positive result of urine pregnancy test.
8. used the same kind of drugs within 48 hours before entering the group.
9. need to continue the combination of the following drugs that have an effect on treatment during the study: NSAIDs, corticosteroids, heparin, warfarin and vitamin K, platelet antagonists or other hemostatic agents.
10. participated in a clinical trial with an investigational drug or device within the past three months.
11. had alcoholic intemperance, drug addiction or other factors that researchers think it unfit for drug clinical trials.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ilaprazole	Drug: Ilaprazole; 10 mg ilaprazole daily (at day 1-3) through intravenous infusion within 30min with first dose doubling.; Drug: Ilaprazole tablet; Since 4th day, those patients were changed to take oral ilaprazole tablets 10mg each day till 30th day; Drug: amoxicillin and clarithromycin; The Patients who with helicobacter pylori infection were provided amoxicillin and clarithromycin as complimentary therapy for two weeks
Active Comparator: omeprazole	Drug: Ilaprazole tablet; Since 4th day, those patients were changed to take oral ilaprazole tablets 10mg each day till 30th day; Drug: amoxicillin and clarithromycin; The Patients who with helicobacter pylori infection were provided amoxicillin and clarithromycin as complimentary therapy for two weeks; Drug: Omeprazole; 40 mg omeprazole twice daily (at day 1-3) through intravenous infusion within 30min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of hemostasis	the hemostasis rate checked by endoscopy within 72 hours	72 hours

Collaborators and Investigators

• Sponsor: Livzon Pharmaceutical Group Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 3, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): December 6, 2017
• Last Update Submitted That Met QC Criteria: December 4, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Proton Pump Inhibitor; Peptic ulcer hemorrhage
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Duodenal Diseases; Gastrointestinal Hemorrhage; Ulcer; Hemorrhage; Peptic Ulcer; Peptic Ulcer Hemorrhage; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Clarithromycin; Omeprazole
• Other Study ID Numbers: Livzon-IYI-Ⅲ

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No