A Safety and Efficacy Study of Lansoprazole in Preventing Aspirin-Induced Gastric and Duodenal Ulcers

Study Overview
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Brief Summary
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The purpose of this study is to determine whether lansoprazole, once daily (QD), compared to gefarnate, twice daily (BID), is effective in preventing the recurrence of gastric and duodenal ulcers in patients receiving long term treatment with low dosage aspirin.

Detailed Description
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In Japan, low-dose aspirin is one of the commonly prescribed drugs for inhibiting thrombosis and thrombus formation after angina, myocardial infarction, ischemic cerebrovascular disease, coronary artery by-pass surgery and percutaneous transluminal coronary angioplasty in patients. While low-dose aspirin is effective in these cases, its use sometimes causes gastric and duodenal ulcers which can lead to gastrointestinal bleeding, and in worse cases may lead to death. The purpose of this study is to assess the efficacy of lansoprazole versus gefarnate in patients with a history of gastric or duodenal ulcers receiving daily low dose aspirin therapy.

Official Title
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A Study to Investigate the Preventive Effect of AG-1749 Against the Recurrence of Gastric And Duodenal Ulcers During Long-Term Treatment With Low Dose Aspirin.

Conditions
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Stomach Ulcer, Duodenal Ulcer

Intervention / Treatment
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* Drug: Lansoprazole
* Drug: Gefarnate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient was on low-dose aspirin treatment on the day when consent was obtained, and requires the long-term continuous treatment even after treatment with the investigational drug is started. The patient was confirmed to have a history of gastric ulcer or duodenal ulcer. Exclusion Criteria: Endoscopically confirmed gastric and/or duodenal ulcers on Day 1. Endoscopically confirmed active upper gastrointestinal hemorrhage on Day 1. Current or past history of aspirin-induced asthma or hypersensitivity to nonsteroidal anti-inflammatory drugs. Past or planned surgery affecting gastric acid secretion. Clinically significant hepatic or renal disorder.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lansoprazole 15 mg QD<br> | Drug: Lansoprazole<br>* Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 12 to 30 months.<br>* Other names: Takepron®;|
| Active Comparator: Gefarnate 50 mg BID<br> | Drug: Gefarnate<br>* Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 12 to 30 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Gastric Ulcer and/or Duodenal Ulcer | The number of participants that developed gastric ulcer and/or duodenal ulcer at month 18 or final visit. Ulcers are defined as mucosal defect with white coating 3 mm or greater. | 18 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 3. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 6. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 9) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 9. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 12. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 18. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 3. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 6. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 9) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 9. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 12. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 18. | 
| Number of Participants With Gastric or Duodenal Ulcer or Gastric or Duodenal Hemorrhagic Lesion (Upper Gastrointestinal Hemorrhage) | Number of participants with gastric or duodenal ulcer or gastric or duodenal hemorrhagic lesion (upper gastrointestinal hemorrhage) from baseline through month 18 or final visit. Ulcers are defined as mucosal defect with white coating 3 mm or greater. | 18 Months | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 3) | Postprandial pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 6) | Postprandial pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 9) | Postprandial pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 12) | Postprandial pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 18) | Postprandial pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 3) | Hunger and nighttime pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 6) | Hunger and nighttime pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 9) | Hunger and nighttime pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 12) | Hunger and nighttime pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 18) | Hunger and nighttime pain is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 3) | Feeling of enlarged abdomen is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 6) | Feeling of enlarged abdomen is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 9) | Feeling of enlarged abdomen is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 12) | Feeling of enlarged abdomen is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 18) | Feeling of enlarged abdomen is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 3) | Feeling of nausea is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 6) | Feeling of nausea is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 9) | Feeling of nausea is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 12) | Feeling of nausea is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 18) | Feeling of nausea is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 3) | Feeling of heartburn is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 6) | Feeling of heartburn is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 9) | Feeling of heartburn is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 12) | Feeling of heartburn is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 18) | Feeling of heartburn is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 3) | Severity of anorexia is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 6) | Severity of anorexia is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 9) | Severity of anorexia is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 12) | Severity of anorexia is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 18) | Severity of anorexia is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 3) | Severity of hematemesis and melena (blood stool, black stool, tarry stool) is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 6) | Severity of hematemesis and melena (blood stool, black stool, tarry stool) is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 9) | Severity of hematemesis and melena (blood stool, black stool, tarry stool) is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 9. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 12) | Severity of hematemesis and melena (blood stool, black stool, tarry stool) is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 18) | Severity of hematemesis and melena (blood stool, black stool, tarry stool) is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Number of Participants With Adverse Events | Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug. A TEAE may also be a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing. Please see Other Adverse Events table below for TEAE listings. | 18 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Curling Ulcer, Gastric Ulcer, Aspirin, Acetylsalicylic Acid, Drug Therapy