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

Duodenal Ulcer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00762359
• Other study ID #: AG-1749-CCT-351
• Secondary ID: 070494U1111-1113
• Status: Terminated
• Phase: Phase 3
• First received: September 26, 2008
• Last updated: February 1, 2012
• Start date: May 2007
• Est. completion date: November 2008

Study information

• Verified date: February 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 461
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Duodenal Ulcer
• Stomach Ulcer
• Ulcer

Intervention

Drug:
• Lansoprazole
Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 12 to 30 months.
• Gefarnate
Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 12 to 30 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No