Gastric or Duodenal Ulcers Caused by Low-dose Aspirin
Conditions
Keywords
Rabeprazole, proton pump inhibitor, Acetylsalicylic Acid, Aspirin, Gastric Ulcer, Duodenal Ulcer
Brief summary
The primary objective of this study to evaluate the effect of preventing recurrence of gastric or duodenal ulcers by administering E3810 5 mg or 10 mg tablets once daily or Teprenone 150 mg/day (50 mg three times daily) as a control to patients receiving low-dose aspirin and thereby examine the superiority of E3810 over Teprenone.
Interventions
DRUGE3810
E3810 5 mg/day Group: Orally administered E3810 5 mg tablets and E3810 10 mg placebo tablets once daily after breakfast; and orally administered Teprenone 50 mg placebo capsules three times daily after each meal.
DRUGTeprenone
Teprenone 150 mg/day Group: Orally administered E3810 5 mg placebo tablets and 10 mg placebo tablets once daily after breakfast; and orally administered Teprenone 50 mg capsules three times daily after each meal.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Require long-term administration of low-dose aspirin (81 mg/day or 100 mg/day) * Confirmed to have a history of gastric or duodenal ulcer
Exclusion criteria
-Confirmed to have acute gastro duodenal mucosal lesions, gastric or duodenal ulcer, or upper gastrointestinal (esophagus, stomach, duodenum) bleeding Confirmed to have reflux esophagitis or long segment Barrett's esophagus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Recurrent Rates of Gastric or Duodenal Ulcers | 24 weeks | Mucosal injuries with a white coat measuring 3 mm in diameter will be diagnosed as ulcers. When ulcer is confirmed by endoscopic examination during the trial, it will be regarded as recurrence of ulcer and the trial will be discontinued for the patient involved. |
Secondary
| Measure | Time frame |
|---|---|
| Cumulative Incidence of Bleeding Ulcers | 24 weeks |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rabeprazole 5 mg Orally administered E3810 (Rabeprazole) 5mg tablet and E3810 10mg placebo tablet once daily after breakfast; and orally administered Teprenone 50mg placebo capsule three times daily after each meal. | 156 |
| Rabeprazole 10 mg Orally administered E3810 (Rabeprazole) 5mg placebo tablet and 10mg tablet once daily after breakfast; and orally administered Teprenone 50mg placebo capsule three times daily after each meal. | 157 |
| Teprenone 150 mg Orally administered E3810 (Rabeprazole) 5mg placebo tablet and 10mg placebo tablet once daily after breakfast; and orally administered Teprenone 50mg capsule three times daily after each meal. | 158 |
| Total | 471 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 6 |
| Overall Study | Lack of Efficacy | 2 | 0 | 5 |
| Overall Study | Other | 8 | 7 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 3 |
Baseline characteristics
| Characteristic | Rabeprazole 5 mg | Total | Teprenone 150 mg | Rabeprazole 10 mg |
|---|---|---|---|---|
| Age, Continuous | 69.3 Years STANDARD_DEVIATION 8.9 | 69.6 Years STANDARD_DEVIATION 8.8 | 69.4 Years STANDARD_DEVIATION 7.9 | 70.1 Years STANDARD_DEVIATION 9.6 |
| Antiplatelet Drug or Anticoagulant Drug No | 126 Participants | 372 Participants | 123 Participants | 123 Participants |
| Antiplatelet Drug or Anticoagulant Drug Yes | 30 Participants | 99 Participants | 35 Participants | 34 Participants |
| Daily Dose of Low-Dose Aspirin 100 mg | 144 Participants | 429 Participants | 142 Participants | 143 Participants |
| Daily Dose of Low-Dose Aspirin 81 mg | 12 Participants | 42 Participants | 16 Participants | 14 Participants |
| Diagnostic Test of H.pylori. (IgG Antibody) Negative | 84 Participants | 255 Participants | 81 Participants | 90 Participants |
| Diagnostic Test of H.pylori. (IgG Antibody) Positive | 72 Participants | 216 Participants | 77 Participants | 67 Participants |
| Primary Disease Angina Pectoris (No) | 88 Participants | 274 Participants | 92 Participants | 94 Participants |
| Primary Disease Angina Pectoris (Yes) | 68 Participants | 197 Participants | 66 Participants | 63 Participants |
| Primary Disease Coronary Arterial Bypass Grafting or PTCA (No) | 104 Participants | 320 Participants | 110 Participants | 106 Participants |
| Primary Disease Coronary Arterial Bypass Grafting or PTCA (Yes) | 52 Participants | 151 Participants | 48 Participants | 51 Participants |
| Primary Disease Ischemic Cerebrovascular Disease (No) | 77 Participants | 237 Participants | 80 Participants | 80 Participants |
| Primary Disease Ischemic Cerebrovascular Disease (Yes) | 79 Participants | 234 Participants | 78 Participants | 77 Participants |
| Primary Disease Myocardial Infarction (No) | 129 Participants | 380 Participants | 125 Participants | 126 Participants |
| Primary Disease Myocardial Infarction (Yes) | 27 Participants | 91 Participants | 33 Participants | 31 Participants |
| Primary Disease Other (No) | 150 Participants | 446 Participants | 149 Participants | 147 Participants |
| Primary Disease Other (Yes) | 6 Participants | 25 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Female | 35 Participants | 112 Participants | 41 Participants | 36 Participants |
| Sex: Female, Male Male | 121 Participants | 359 Participants | 117 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 156 | 46 / 157 | 41 / 158 |
| serious Total, serious adverse events | 10 / 156 | 6 / 157 | 10 / 158 |
Outcome results
Primary
Cumulative Recurrent Rates of Gastric or Duodenal Ulcers
Mucosal injuries with a white coat measuring 3 mm in diameter will be diagnosed as ulcers. When ulcer is confirmed by endoscopic examination during the trial, it will be regarded as recurrence of ulcer and the trial will be discontinued for the patient involved.
Time frame: 24 weeks
Population: Defined as all randomized participants who received at least one dose of the study drug and showed no ulcers at baseline, and from whom the results of at least one endoscopic assessment was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole 5 mg | Cumulative Recurrent Rates of Gastric or Duodenal Ulcers | 2.8 Events/100 participants/24 weeks |
| Rabeprazole 10 mg | Cumulative Recurrent Rates of Gastric or Duodenal Ulcers | 1.4 Events/100 participants/24 weeks |
| Teprenone 150 mg | Cumulative Recurrent Rates of Gastric or Duodenal Ulcers | 21.7 Events/100 participants/24 weeks |
p-value: <0.00195% CI: [0.04, 0.31]Log Rank
p-value: <0.00195% CI: [0.01, 0.23]Log Rank
Secondary
Cumulative Incidence of Bleeding Ulcers
Time frame: 24 weeks
Population: Defined as all randomized participants who received at least one dose of the study drug and showed no ulcers at baseline, and from whom the results of at least one endoscopic assessment was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabeprazole 5 mg | Cumulative Incidence of Bleeding Ulcers | 0 Events/100 participants/24 weeks |
| Rabeprazole 10 mg | Cumulative Incidence of Bleeding Ulcers | 0 Events/100 participants/24 weeks |
| Teprenone 150 mg | Cumulative Incidence of Bleeding Ulcers | 4.6 Events/100 participants/24 weeks |