Gastric Ulcer, Duodenal Ulcer
Conditions
Keywords
Peptic ulcer, low-dose ASA
Brief summary
The purpose of this study is to compare the effect of esomeprazole 20 or 40 mg once daily versus placebo on the occurrence of peptic ulcers during 26 weeks in subjects on continuous low-dose acetylsalicylic acid.
Interventions
Esomeprazole 40 mg once daily
Esomeprazole 20 mg once daily
DRUGPlacebo
Placebo once daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Daily intake of low-dose Aspirin (ASA) - The subject must fulfill at least one of the following (a-e): * Aged ≥65 years. * Aged ≥18 years and with a documented history of uncomplicated peptic ulcer(s). * Aged ≥60 years and naïve to low-dose ASA (ie, treatment started within 1 month prior to randomization). * Aged ≥60 years and with stable coronary artery disease. * Aged ≥60 years and with complaints of upper gastrointestinal (GI) symptoms that, as judged by the investigator, requires an Esophagogastroduodenoscopy (EGD) and with the finding of ≥5 gastric and/or duodenal erosions at the baseline endoscopy.
Exclusion criteria
* Peptic ulcer(s) at baseline esophagogastroduodenoscopy (EGD). * Reflux esophagitis Los Angeles (LA) classification grade C or D at baseline * History of peptic ulcer complications such as clinically significant bleeding and/or perforation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced the Occurence of Peptic Ulcer(s). | During 26 weeks | The occurrence of ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced the Occurence of Gastric Ulcer. | During 26 weeks | The occurrence of gastric ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal. |
| Percentage of Participants Who Experienced the Occurrence of Duodenal Ulcer. | During 26 weeks | The occurrence of duodenal ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal. |
| Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Dyspepsia Dimension During the 26-week Visit or the Week Prior to the Last Visit. | RDQ was assessed at baseline, 8 weeks, 16 week, 26 weeks or upon withdrawal. | RDQ contains 12 items on a 6-point Likert scale. Six items concern the frequence ('Did not have' to 'Daily') and six items concern the severity ('Did not have' to 'Severe'). The dyspepsia dimension contains the items 'Burning feeling in the center of the upper stomach' and 'Pain in the center of the upper stomach'. Best score possible 0, worst score possible - daily occurrence. |
| Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Gastroesophageal Reflux Disease Dimension During the 26-week Visit or the Week Prior to the Last Visit. | RDQ was assessed at baseline, 8 weeks, 16 week, 26 weeks or upon withdrawal. | RDQ contains 12 items on a 6-point Likert scale. Six items concern the frequency ('Did not have' to 'Daily') and six items concern the severity ('Did not have' to 'Severe'). Gastroesophageal reflux disease (GERD) items: 'Acid taste in the mouth', 'Unpleasant movement of materials upward from the stomach', 'Burning feeling behind the breastbone' and 'Pain behind the breastbone'. Best score possible 0, worst score possible - daily occurrence. |
| Number of Participants With Gastric and/or Duodenal Erosions. | The number of erosions was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal. | — |
Countries
Argentina, Australia, Bulgaria, Canada, Czechia, Finland, Germany, Indonesia, Mexico, Norway, Philippines, Poland, Portugal, Romania, Russia, Slovakia, South Africa, South Korea, Thailand, United States
Participant flow
Recruitment details
The first subject was randomized 22 February 2007 and last subject completed 28 August 2008. Cardiologists, primary care physicians and gastroenterologists were the primary target investigators.
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole 40 Esomeprazole 40 mg every day for 26 weeks in subjects on continuous low-dose ASA (acetylsalicyclic acid) (75-325 mg) | 817 |
| Esomeproazole 20 Esomeprazole 20 mg every day for 26 weeks in subjects on continuous low dose ASA (75-325 mg) | 804 |
| Placebo Placebo every day for 26 weeks in subjects on continuous low-dose ASA (75-325 mg) | 805 |
| Total | 2,426 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 26 | 33 | 28 |
| Overall Study | Lack of Efficacy | 7 | 8 | 48 |
| Overall Study | Lost to Follow-up | 5 | 6 | 5 |
| Overall Study | Protocol Violation | 19 | 28 | 32 |
| Overall Study | Safety Reasons | 3 | 1 | 3 |
| Overall Study | Various reason specified | 6 | 8 | 5 |
| Overall Study | Withdrawal by Subject | 40 | 34 | 47 |
Baseline characteristics
| Characteristic | Esomeprazole 40 | Esomeproazole 20 | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 577 Participants | 558 Participants | 545 Participants | 1680 Participants |
| Age, Categorical Between 18 and 65 years | 240 Participants | 246 Participants | 260 Participants | 746 Participants |
| Sex: Female, Male Female | 380 Participants | 375 Participants | 402 Participants | 1157 Participants |
| Sex: Female, Male Male | 437 Participants | 429 Participants | 403 Participants | 1269 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 | 32 / — | 42 / — | 31 / — |
| serious Total, serious adverse events | 46 / — | 40 / — | 35 / — |
Outcome results
Primary
Percentage of Participants Who Experienced the Occurence of Peptic Ulcer(s).
The occurrence of ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.
Time frame: During 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 | Percentage of Participants Who Experienced the Occurence of Peptic Ulcer(s). | 1.35 percentage of participants |
| Esomeproazole 20 | Percentage of Participants Who Experienced the Occurence of Peptic Ulcer(s). | 1 percentage of participants |
| Placebo | Percentage of Participants Who Experienced the Occurence of Peptic Ulcer(s). | 6.58 percentage of participants |
Secondary
Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Dyspepsia Dimension During the 26-week Visit or the Week Prior to the Last Visit.
RDQ contains 12 items on a 6-point Likert scale. Six items concern the frequence ('Did not have' to 'Daily') and six items concern the severity ('Did not have' to 'Severe'). The dyspepsia dimension contains the items 'Burning feeling in the center of the upper stomach' and 'Pain in the center of the upper stomach'. Best score possible 0, worst score possible - daily occurrence.
Time frame: RDQ was assessed at baseline, 8 weeks, 16 week, 26 weeks or upon withdrawal.
Population: Patients randomized who took at least one dose of study drug and completed RDQ questionnaire at baseline and at week 26 or the week prior to last visit were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 | Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Dyspepsia Dimension During the 26-week Visit or the Week Prior to the Last Visit. | 591 participants |
| Esomeproazole 20 | Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Dyspepsia Dimension During the 26-week Visit or the Week Prior to the Last Visit. | 577 participants |
| Placebo | Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Dyspepsia Dimension During the 26-week Visit or the Week Prior to the Last Visit. | 504 participants |
Secondary
Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Gastroesophageal Reflux Disease Dimension During the 26-week Visit or the Week Prior to the Last Visit.
RDQ contains 12 items on a 6-point Likert scale. Six items concern the frequency ('Did not have' to 'Daily') and six items concern the severity ('Did not have' to 'Severe'). Gastroesophageal reflux disease (GERD) items: 'Acid taste in the mouth', 'Unpleasant movement of materials upward from the stomach', 'Burning feeling behind the breastbone' and 'Pain behind the breastbone'. Best score possible 0, worst score possible - daily occurrence.
Time frame: RDQ was assessed at baseline, 8 weeks, 16 week, 26 weeks or upon withdrawal.
Population: Patients randomized who took at least one dose of study drug and completed RDQ questionnaire at baseline and at week 26 or the week prior to last visit were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 | Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Gastroesophageal Reflux Disease Dimension During the 26-week Visit or the Week Prior to the Last Visit. | 554 participants |
| Esomeproazole 20 | Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Gastroesophageal Reflux Disease Dimension During the 26-week Visit or the Week Prior to the Last Visit. | 537 participants |
| Placebo | Number of Participants Reporting 0 in the Dichotomized RDQ (Reflux and Disease Questionnaire) Score (0 Versus >0) for the Gastroesophageal Reflux Disease Dimension During the 26-week Visit or the Week Prior to the Last Visit. | 451 participants |
Secondary
Number of Participants With Gastric and/or Duodenal Erosions.
Time frame: The number of erosions was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.
Population: Patients randomized who had endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 | Number of Participants With Gastric and/or Duodenal Erosions. | 214 participants |
| Esomeproazole 20 | Number of Participants With Gastric and/or Duodenal Erosions. | 213 participants |
| Placebo | Number of Participants With Gastric and/or Duodenal Erosions. | 380 participants |
Secondary
Percentage of Participants Who Experienced the Occurence of Gastric Ulcer.
The occurrence of gastric ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.
Time frame: During 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 | Percentage of Participants Who Experienced the Occurence of Gastric Ulcer. | 1.1 percentage of participants |
| Esomeproazole 20 | Percentage of Participants Who Experienced the Occurence of Gastric Ulcer. | 0.75 percentage of participants |
| Placebo | Percentage of Participants Who Experienced the Occurence of Gastric Ulcer. | 4.1 percentage of participants |
Secondary
Percentage of Participants Who Experienced the Occurrence of Duodenal Ulcer.
The occurrence of duodenal ulcer (mucosal break measuring \>= 3 mm over its largest diameter with a sharply demarcated margin) was determined by endoscopy performed at baseline, 8 weeks and 26 weeks or upon withdrawal.
Time frame: During 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esomeprazole 40 | Percentage of Participants Who Experienced the Occurrence of Duodenal Ulcer. | 0.24 percentage of participants |
| Esomeproazole 20 | Percentage of Participants Who Experienced the Occurrence of Duodenal Ulcer. | 0.25 percentage of participants |
| Placebo | Percentage of Participants Who Experienced the Occurrence of Duodenal Ulcer. | 2.73 percentage of participants |