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

Phase 3
Terminated
Conditions
Stomach Ulcer
Duodenal Ulcer
Interventions
Registration Number
NCT00762359
Lead Sponsor
Takeda
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
461
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Lansoprazole 15 mg QDLansoprazole-
Gefarnate 50 mg BIDGefarnate-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Gastric Ulcer and/or Duodenal Ulcer18 Months

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3)Baseline and 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.

Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6)Baseline and 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.

Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 9)Baseline and 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.

Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12)Baseline and 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.

Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18)Baseline and 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.

Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3)Baseline and 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.

Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6)Baseline and 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.

Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 18)Baseline and 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.

Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 9)Baseline and 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.

Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12)Baseline and 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.

Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18)Baseline and 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.

Number of Participants With Gastric or Duodenal Ulcer or Gastric or Duodenal Hemorrhagic Lesion (Upper Gastrointestinal Hemorrhage)18 Months

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.

Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 18)Baseline and 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.

Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 18)Baseline and 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.

Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 18)Baseline and 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.

Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 18)Baseline and 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.

Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 18)Baseline and 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.

Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 3)Baseline and 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.

Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 6)Baseline and 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.

Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 9)Baseline and 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.

Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 12)Baseline and 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.

Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 18)Baseline and 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.

Number of Participants With Adverse Events18 Months

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.

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