Prevention of Recurrent Gastric or Duodenal Ulcers Caused by Low-dose Aspirin With Rabeprazole (E3810) Treatment (Planetarium Study)
Sponsor
Eisai Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT01397448
Collaborator
(none)
472
49
3
23
9.6
0.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
472 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Prevention of Recurrent Gastric or Duodenal Ulcers Caused by Low-dose Aspirin With Rabeprazole (E3810) Treatment. - A Multicenter, Randomized, Parallel-group, Double-blind Comparative Trial-
Study Start Date
:
Jul 1, 2011
Actual Primary Completion Date
:
Mar 1, 2013
Actual Study Completion Date
:
Jun 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: E3810 5 mg
|
Drug: E3810
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.
|
| Experimental: E3810 10 mg
|
Drug: E3810
E3810 10 mg Group: Orally administered E3810 5 mg placebo tablets and 10 mg tablets once daily after breakfast; and orally administered Teprenone 50 mg placebo capsules three times daily after each meal.
|
| Active Comparator: Teprenone 150 mg
|
Drug: Teprenone
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Cumulative Incidence of Bleeding Ulcers [24 weeks]
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kasugai | Aichi | Japan | ||
| 2 | Nagoya | Aichi | Japan | ||
| 3 | Ichikawa | Chiba | Japan | ||
| 4 | Chikushino | Fukuoka | Japan | ||
| 5 | Kitakyushu | Fukuoka | Japan | ||
| 6 | Onga | Fukuoka | Japan | ||
| 7 | Maebashi | Gunma | Japan | ||
| 8 | Asahikawa | Hokkaido | Japan | ||
| 9 | Sapporo | Hokkaido | Japan | ||
| 10 | Tomakomai | Hokkaido | Japan | ||
| 11 | Itami | Hyogo | Japan | ||
| 12 | Kobe | Hyogo | Japan | ||
| 13 | Hitachi | Ibaraki | Japan | ||
| 14 | Fujisawa | Kanagawa | Japan | ||
| 15 | Kawasaki | Kanagawa | Japan | ||
| 16 | Sagamihara | Kanagawa | Japan | ||
| 17 | Yokohama | Kanagawa | Japan | ||
| 18 | Hitoyoshi | Kumamoto | Japan | ||
| 19 | Ebino | Miyazaki | Japan | ||
| 20 | Chikuma | Nagano | Japan | ||
| 21 | Matsumoto | Nagano | Japan | ||
| 22 | Suzaka | Nagano | Japan | ||
| 23 | Beppu | Oita | Japan | ||
| 24 | Yufu | Oita | Japan | ||
| 25 | Daito | Osaka | Japan | ||
| 26 | Hirakata | Osaka | Japan | ||
| 27 | Matsubara | Osaka | Japan | ||
| 28 | Takatsuki | Osaka | Japan | ||
| 29 | Yao | Osaka | Japan | ||
| 30 | Karatsu | Saga | Japan | ||
| 31 | Ureshino | Saga | Japan | ||
| 32 | Izumo | Shimane | Japan | ||
| 33 | Hamamatsu | Shizuoka | Japan | ||
| 34 | Ohtawara | Tochigi | Japan | ||
| 35 | Mitaka | Tokyo | Japan | ||
| 36 | Setagaya | Tokyo | Japan | ||
| 37 | Shinjuku | Tokyo | Japan | ||
| 38 | Fukuoka | Japan | |||
| 39 | Gifu | Japan | |||
| 40 | Kochi | Japan | |||
| 41 | Kumamoto | Japan | |||
| 42 | Kyoto | Japan | |||
| 43 | Miyazaki | Japan | |||
| 44 | Nagano | Japan | |||
| 45 | Nagasaki | Japan | |||
| 46 | Oita | Japan | |||
| 47 | Osaka | Japan | |||
| 48 | Saga | Japan | |||
| 49 | Shizuoka | Japan |
Sponsors and Collaborators
- Eisai Co., Ltd.
Investigators
- Study Director: Nobuyuki Sugisaki, Japan/Asia Clinical Research Product Creation Unit
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eisai Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01397448
Other Study ID Numbers:
- E3810-J081-308
First Posted:
Jul 19, 2011
Last Update Posted:
Nov 26, 2014
Last Verified:
Oct 1, 2014
Keywords provided by Eisai Co., Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Period Title: Overall Study | |||
| STARTED | 156 | 157 | 158 |
| COMPLETED | 138 | 142 | 140 |
| NOT COMPLETED | 18 | 15 | 18 |
Baseline Characteristics
| Arm/Group Title | Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 156 | 157 | 158 | 471 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
69.3
(8.9)
|
70.1
(9.6)
|
69.4
(7.9)
|
69.6
(8.8)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
35
22.4%
|
36
22.9%
|
41
25.9%
|
112
23.8%
|
| Male |
121
77.6%
|
121
77.1%
|
117
74.1%
|
359
76.2%
|
| Antiplatelet Drug or Anticoagulant Drug (Number) [Number] | ||||
| Yes |
30
19.2%
|
34
21.7%
|
35
22.2%
|
99
21%
|
| No |
126
80.8%
|
123
78.3%
|
123
77.8%
|
372
79%
|
| Daily Dose of Low-Dose Aspirin (Number) [Number] | ||||
| 81 mg |
12
7.7%
|
14
8.9%
|
16
10.1%
|
42
8.9%
|
| 100 mg |
144
92.3%
|
143
91.1%
|
142
89.9%
|
429
91.1%
|
| Diagnostic Test of H.pylori. (IgG Antibody) (Number) [Number] | ||||
| Positive |
72
46.2%
|
67
42.7%
|
77
48.7%
|
216
45.9%
|
| Negative |
84
53.8%
|
90
57.3%
|
81
51.3%
|
255
54.1%
|
| Primary Disease (Number) [Number] | ||||
| Angina Pectoris (Yes) |
68
43.6%
|
63
40.1%
|
66
41.8%
|
197
41.8%
|
| Angina Pectoris (No) |
88
56.4%
|
94
59.9%
|
92
58.2%
|
274
58.2%
|
| Myocardial Infarction (Yes) |
27
17.3%
|
31
19.7%
|
33
20.9%
|
91
19.3%
|
| Myocardial Infarction (No) |
129
82.7%
|
126
80.3%
|
125
79.1%
|
380
80.7%
|
| Ischemic Cerebrovascular Disease (Yes) |
79
50.6%
|
77
49%
|
78
49.4%
|
234
49.7%
|
| Ischemic Cerebrovascular Disease (No) |
77
49.4%
|
80
51%
|
80
50.6%
|
237
50.3%
|
| Coronary Arterial Bypass Grafting or PTCA (Yes) |
52
33.3%
|
51
32.5%
|
48
30.4%
|
151
32.1%
|
| Coronary Arterial Bypass Grafting or PTCA (No) |
104
66.7%
|
106
67.5%
|
110
69.6%
|
320
67.9%
|
| Other (Yes) |
6
3.8%
|
10
6.4%
|
9
5.7%
|
25
5.3%
|
| Other (No) |
150
96.2%
|
147
93.6%
|
149
94.3%
|
446
94.7%
|
Outcome Measures
| Title | Cumulative Incidence of Bleeding Ulcers |
|---|---|
| Description | |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 150 | 151 | 151 |
| Number (95% Confidence Interval) [Events/100 participants/24 weeks] |
0
0%
|
0
0%
|
4.6
2.9%
|
| Title | Cumulative Recurrent Rates of Gastric or Duodenal Ulcers |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 150 | 151 | 151 |
| Number (95% Confidence Interval) [Events/100 participants/24 weeks] |
2.8
1.8%
|
1.4
0.9%
|
21.7
13.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rabeprazole 5 mg, Teprenone 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.11 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 0.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rabeprazole 10 mg, Teprenone 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% 0.01 to 0.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | 24 weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/156 (6.4%) | 6/157 (3.8%) | 10/158 (6.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 1/156 (0.6%) | 0/157 (0%) | 2/158 (1.3%) | |||
| Gastrointestinal disorders | ||||||
| Duodenal ulcer | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Duodenal ulcer haemorrhage | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Gastric ulcer haemorrhage | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Gastrointestinal haemorrhage | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Pancreatitis acute | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Vomiting | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| General disorders | ||||||
| Chest discomfort | 0/156 (0%) | 1/157 (0.6%) | 0/158 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 0/156 (0%) | 1/157 (0.6%) | 0/158 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Pneumonia mycoplasmal | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Injury, poisoning and procedural complications | ||||||
| Spinal compression fracture | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Subdural haematoma | 0/156 (0%) | 1/157 (0.6%) | 0/158 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus inadequate control | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Hypoglycaemia | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Polymyalgia rheumatica | 0/156 (0%) | 1/157 (0.6%) | 0/158 (0%) | |||
| Rotator cuff syndrome | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Bile duct cancer | 0/156 (0%) | 1/157 (0.6%) | 0/158 (0%) | |||
| Lung neoplasm malignant | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Gastric adenoma | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
| Nervous system disorders | ||||||
| Carotid artery stenosis | 0/156 (0%) | 1/157 (0.6%) | 0/158 (0%) | |||
| Carpal tunnel syndrome | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Embolic stroke | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Renal and urinary disorders | ||||||
| Renal artery stenosis | 0/156 (0%) | 0/157 (0%) | 1/158 (0.6%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pneumonia aspiration | 1/156 (0.6%) | 0/157 (0%) | 0/158 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Rabeprazole 5 mg | Rabeprazole 10 mg | Teprenone 150 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 48/156 (30.8%) | 46/157 (29.3%) | 41/158 (25.9%) | |||
| Gastrointestinal disorders | ||||||
| Constipation | 1/156 (0.6%) | 5/157 (3.2%) | 6/158 (3.8%) | |||
| Diarrhoea | 4/156 (2.6%) | 6/157 (3.8%) | 2/158 (1.3%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 25/156 (16%) | 22/157 (14%) | 25/158 (15.8%) | |||
| Pharyngitis | 6/156 (3.8%) | 1/157 (0.6%) | 2/158 (1.3%) | |||
| Upper respiratory tract infection | 5/156 (3.2%) | 3/157 (1.9%) | 2/158 (1.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 4/156 (2.6%) | 0/157 (0%) | 3/158 (1.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 4/156 (2.6%) | 2/157 (1.3%) | 1/158 (0.6%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Epistaxis | 0/156 (0%) | 1/157 (0.6%) | 4/158 (2.5%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Eczema | 1/156 (0.6%) | 6/157 (3.8%) | 1/158 (0.6%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/156 (0%) | 5/157 (3.2%) | 3/158 (1.9%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Nobuyuki Sugisaki |
|---|---|
| Organization | Eisai Co., Ltd. |
| Phone | +81-3-3817-3908 ext 3908 |
Responsible Party:
Eisai Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01397448
Other Study ID Numbers:
- E3810-J081-308
First Posted:
Jul 19, 2011
Last Update Posted:
Nov 26, 2014
Last Verified:
Oct 1, 2014