Long-term Use of Takepron Capsules on the Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Low-dose Aspirin

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02099682
• Collaborator: (none)
• Enrollment: 3,366
• Duration (Months): 41

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and efficacy of long-term administration of lansoprazole (Takepron) for up to 12 months in the routine clinical setting in patients receiving low-dose aspirin

Condition or Disease	Intervention/Treatment	Phase
Gastric or Duodenal Ulcers	Drug: Lansoprazole

Detailed Description

This is a special survey on long-term use (for up to 12 months) of lansoprazole (Takepron) to determine the incidence of adverse drug reactions in the routine clinical setting in patients receiving low-dose aspirin.

The usual adult dosage is 15 mg of lansoprazole administered orally once daily.

Study Design

• Study Type: Observational
• Actual Enrollment: 3366 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Takepron Capsules 15/ Orally Dispersing (OD) Tablets 15 Special Drug Use Surveillance Long-term Use Survey on the Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Low-dose Aspirin
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Lansoprazole 15 mg Lansoprazole 15 mg orally once daily	Drug: Lansoprazole; Lansoprazole Capsules 15/ OD Tablets; Other Names: Takepron Capsules 15/ OD Tablets

Outcome Measures

Primary Outcome Measures

1. Frequency of Adverse Drug Reactions [12 months]

   Frequency, severity, and time to onset of adverse drug reactions tabulated by each symptom. Adverse events are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.

Secondary Outcome Measures

1. Presence or Absence of Endoscopic Examinations [From baseline to 12 months]

   Summary of data on the presence or absence of endoscopic examinations.

2. Presence of Gastric or Duodenal Ulcer [From baseline to 12 months]

   Summary of data on the presence or absence of gastric or duodenal ulcers.

3. Presence of Gastric or Duodenal Hemorrhagic Lesion [From baseline to 12 months]

   Summary of data on the presence or absence of gastric or duodenal hemorrhagic lesions.

4. Presence of Either Gastric/Duodenal Ulcer, or Gastric/Duodenal Hemorrhagic Lesion [From baseline to 12 months]

   Summary of data on the presence or absence of gastric/duodenal ulcer gastric/duodenal hemorrhagic lesion.

5. Treatment for Gastric/Duodenal Ulcer or Lesion [From baseline to 12 months]

   Summary of data on the presence or absence of treatment for duodenal ulcers or hemorrhagic lesions.

6. Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions [From baseline to 12 months]

   Summary of data on the details of treatment for gastric or duodenal ulcers or hemorrhagic lesions.

7. Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions [From baseline to 12 months]

   Summary of data on the outcome of treatment for gastric or duodenal ulcers or hemorrhagic lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• (1) Patients with a history of gastric or duodenal ulcers (2) Patients requiring long-term use of low-dose aspirin (81-324 mg once daily) as prophylaxis for thromboembolism (3) Patients taking low-dose oral aspirin (81-324 mg once daily) at the start of administration of lansoprazole (including patients who start low-dose aspirin on the same day as the start of administration of lansoprazole)

Exclusion Criteria:

• (1) Patients with gastric or duodenal ulcer (in the active [A1, A2] or healing [H1, H2] stage if assessed endoscopically) at the start of administration of lansoprazole (2) Patients with active upper gastrointestinal hemorrhage at the start of administration of lansoprazole (3) Patients with contraindications for lansoprazole

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Takeda

Investigators

• Study Chair: Postmarketing Group Manager, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02099682
• Other Study ID Numbers: 467-712; JapicCTI-142414; JapicCTI-R150735
• First Posted: Mar 31, 2014
• Last Update Posted: Nov 4, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Takeda: Pharmacological therapy
• Additional relevant MeSH terms: Duodenal Ulcer; Ulcer; Recurrence; Lansoprazole; Dexlansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 460 investigative sites in Japan from August 2010 to January 2014 (N=3366).
Pre-assignment Detail	Patients with a history of gastric or duodenal ulcers and requiring long-term use of low-dose aspirin were enrolled in the study.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Period Title: Overall Study
STARTED	3366
Safety Analysis Set (SAS)	3255
COMPLETED	3255
NOT COMPLETED	111

Baseline Characteristics

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Overall Participants	3255
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.4 (11.02)
Sex: Female, Male (Count of Participants)
Female	1399 43%
Male	1856 57%
Purpose for Low-Dose Aspirin Use (participants) [Number]
Angina pectoris	1182 36.3%
Myocardial infarction	531 16.3%
Transient ischaemic attack (TIA)	221 6.8%
Cerebral infarction	1225 37.6%
Post-coronary artery bypass (CABG)	106 3.3%
PTCA	398 12.2%
Other	316 9.7%
Gastric or Duodenal Ulcer History Breakdown (participants) [Number]
Gastric ulcer	2718 83.5%
Duodenal ulcer	313 9.6%
Unknown	252 7.7%
Gastric or Duodenal Ulcer History: Time of Onset (participants) [Number]
Within 6 months of study drug administration	213 6.5%
≥ 6 months, < 1 year before start of treatment	138 4.2%
1 year or longer before the start of treatment	977 30%
Unknown	1927 59.2%
H. pylori infection (participants) [Number]
Negative	425 13.1%
Positive	171 5.3%
Unknown	2659 81.7%

Outcome Measures

1. Primary Outcome

Title	Frequency of Adverse Drug Reactions
Description	Frequency, severity, and time to onset of adverse drug reactions tabulated by each symptom. Adverse events are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Safety analysis set - All participants who received at least 1 dose of lansoprazole.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3255
Enteritis infectious	1 0%
Lymphoma	1 0%
Diabetes mellitus	1 0%
Anxiety	1 0%
Dizziness	2 0.1%
Dysgeusia	1 0%
Headache	1 0%
Loss of consciousness	1 0%
Sudden hearing loss	1 0%
Abdominal discomfort	1 0%
Abdominal distension	1 0%
Abdominal pain	1 0%
Colitis	1 0%
Constipation	2 0.1%
Diarrhoea	23 0.7%
Enterocolitis	1 0%
Gastrooesophageal reflux disease	1 0%
Haematochezia	1 0%
Nausea	4 0.1%
Colitis microscopic	3 0.1%
Hypoaesthesia oral	1 0%
Faeces soft	1 0%
Drug eruption	3 0.1%
Eczema	1 0%
Hypersensitivity vasculitis	1 0%
Pruritus	1 0%
Rash generalised	1 0%
Back pain	1 0%
Osteoporosis	1 0%
Renal failure chronic	1 0%
Sudden death	1 0%
Thirst	1 0%
Hepatic enzyme increased	1 0%
Glycosylated haemoglobin increased	1 0%
Weight decreased	1 0%
Fall	1 0%
Spinal fracture	1 0%

2. Secondary Outcome

Title	Presence or Absence of Endoscopic Examinations
Description	Summary of data on the presence or absence of endoscopic examinations.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
With endoscopy	2773 85.2%
Without endoscopy	437 13.4%

3. Secondary Outcome

Title	Presence of Gastric or Duodenal Ulcer
Description	Summary of data on the presence or absence of gastric or duodenal ulcers.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
Present	3190 98%
Absent	20 0.6%

4. Secondary Outcome

Title	Presence of Gastric or Duodenal Hemorrhagic Lesion
Description	Summary of data on the presence or absence of gastric or duodenal hemorrhagic lesions.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
Present	3201 98.3%
Absent	9 0.3%

5. Secondary Outcome

Title	Presence of Either Gastric/Duodenal Ulcer, or Gastric/Duodenal Hemorrhagic Lesion
Description	Summary of data on the presence or absence of gastric/duodenal ulcer gastric/duodenal hemorrhagic lesion.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
Present	3186 97.9%
Absent	24 0.7%

6. Secondary Outcome

Title	Treatment for Gastric/Duodenal Ulcer or Lesion
Description	Summary of data on the presence or absence of treatment for duodenal ulcers or hemorrhagic lesions.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
Present	0 0%
Absent	24 0.7%

7. Secondary Outcome

Title	Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions
Description	Summary of data on the details of treatment for gastric or duodenal ulcers or hemorrhagic lesions.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
Takepron Capsule or OD Tablet 15 mg	15 0.5%
Takepron Capsule or OD Tablet 30 mg	2 0.1%
Rabeprazole tablet 10 mg	2 0.1%
H2 receptor antagonist (oral)	1 0%
Omeprazole (injection)	2 0.1%
H2 receptor antagonist (injection)	1 0%
Other peptic ulcer drugs	2 0.1%
Endoscopic hemostasis	1 0%
Other	5 0.2%

8. Secondary Outcome

Title	Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions
Description	Summary of data on the outcome of treatment for gastric or duodenal ulcers or hemorrhagic lesions.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
Measure Participants	3210
Takepron 15 mg: Recovery	9 0.3%
Takepron 15 mg: Relief	6 0.2%
Takepron 30 mg: Recovery	1 0%
Takepron 30 mg: Relief	1 0%
Rabeprazole 10 mg: Recovery	1 0%
Rabeprazole 10 mg: Relief	1 0%
H2 receptor antagonist (orally): Recovery	1 0%
H2 receptor antagonist (orally): Relief	1 0%
Omeprazole (injection): Recovery	1 0%
Omeprazole (injection): Relief	1 0%
H2 receptor antagonist (injection): Recovery	2 0.1%
H2 receptor antagonist (injection): Relief	1 0%
Other peptic ulcer drugs: Recovery	3 0.1%
Other peptic ulcer drugs: Relief	2 0.1%
Endoscopic hemostasis: Recovery	9 0.3%
Endoscopic hemostasis: Relief	6 0.2%
Other: Recovery	1 0%
Other: Relief	1 0%

Adverse Events

Time Frame	From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months).
Adverse Event Reporting Description	Adverse events are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.
Arm/Group Title	Lansoprazole 15 mg
Arm/Group Description	Lansoprazole 15 mg orally once daily
All Cause Mortality
	Lansoprazole 15 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lansoprazole 15 mg
	Affected / at Risk (%)	# Events
Total	126/3225 (3.9%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/3225 (0%)
Cardiac disorders
Angina pectoris	4/3225 (0.1%)
Angina unstable	2/3225 (0.1%)
Aortic valve stenosis	1/3225 (0%)
Atrial fibrillation	2/3225 (0.1%)
Cardiac failure	8/3225 (0.2%)
Cardiac failure acute	2/3225 (0.1%)
Cardiac failure congestive	6/3225 (0.2%)
Myocardial infarction	5/3225 (0.2%)
Ventricular arrhythmia	1/3225 (0%)
Acute coronary syndrome	1/3225 (0%)
Cardiac failure chronic	1/3225 (0%)
Ear and labyrinth disorders
Sudden hearing loss	1/3225 (0%)
Eye disorders
Cataract	1/3225 (0%)
Gastrointestinal disorders
Abdominal pain	1/3225 (0%)
Colitis ischaemic	2/3225 (0.1%)
Diarrhoea	2/3225 (0.1%)
Gastric polyps	1/3225 (0%)
Gastric ulcer	1/3225 (0%)
Gastritis	1/3225 (0%)
Ileal ulcer	1/3225 (0%)
Inguinal hernia	1/3225 (0%)
Intestinal obstruction	1/3225 (0%)
Melaena	1/3225 (0%)
Pancreatitis acute	1/3225 (0%)
Rectal ulcer	1/3225 (0%)
Large intestine polyp	1/3225 (0%)
Alcoholic pancreatitis	1/3225 (0%)
Haemorrhagic erosive gastritis	1/3225 (0%)
General disorders
Death	2/3225 (0.1%)
Oedema peripheral	1/3225 (0%)
Pyrexia	1/3225 (0%)
Sudden death	1/3225 (0%)
Sudden cardiac death	1/3225 (0%)
Accidental device ingestion	1/3225 (0%)
Hepatobiliary disorders
Bile duct stone	1/3225 (0%)
Cholecystitis	2/3225 (0.1%)
Cholelithiasis	1/3225 (0%)
Hepatic function abnormal	1/3225 (0%)
Liver disorder	1/3225 (0%)
Infections and infestations
Appendicitis	1/3225 (0%)
Gastroenteritis	1/3225 (0%)
Pneumonia	9/3225 (0.3%)
Pyelonephritis	2/3225 (0.1%)
Sepsis	1/3225 (0%)
Urinary tract infection	1/3225 (0%)
Injury, poisoning and procedural complications
Failure to anastomose	1/3225 (0%)
Fall	2/3225 (0.1%)
Femoral neck fracture	1/3225 (0%)
Femur fracture	1/3225 (0%)
Road traffic accident	2/3225 (0.1%)
Subdural haematoma	1/3225 (0%)
Traumatic ulcer	1/3225 (0%)
Traumatic fracture	1/3225 (0%)
Skull fracture	1/3225 (0%)
Musculoskeletal and connective tissue disorders
Muscle haemorrhage	1/3225 (0%)
Spinal osteoarthritis	1/3225 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer	1/3225 (0%)
Breast cancer	1/3225 (0%)
Colon cancer	4/3225 (0.1%)
Gastric cancer	4/3225 (0.1%)
Lymphoma	2/3225 (0.1%)
Rectal cancer	1/3225 (0%)
Uterine cancer	1/3225 (0%)
Colon adenoma	1/3225 (0%)
Lung neoplasm malignant	4/3225 (0.1%)
Non-small cell lung cancer	1/3225 (0%)
Hepatocellular carcinoma	1/3225 (0%)
Nervous system disorders
Carotid artery stenosis	1/3225 (0%)
Cerebellar infarction	1/3225 (0%)
Cerebral haemorrhage	2/3225 (0.1%)
Cerebral infarction	5/3225 (0.2%)
Convulsion	1/3225 (0%)
Dyslalia	1/3225 (0%)
Epilepsy	1/3225 (0%)
Hemiparesis	1/3225 (0%)
Intracranial aneurysm	1/3225 (0%)
Thrombotic cerebral infarction	1/3225 (0%)
Psychiatric disorders
Agitation	1/3225 (0%)
Psychosomatic disease	1/3225 (0%)
Renal and urinary disorders
Renal failure acute	1/3225 (0%)
Renal impairment	1/3225 (0%)
Reproductive system and breast disorders
Breast mass	1/3225 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/3225 (0%)
Chronic obstructive pulmonary disease	1/3225 (0%)
Chronic respiratory failure	1/3225 (0%)
Emphysema	1/3225 (0%)
Interstitial lung disease	1/3225 (0%)
Pleural effusion	1/3225 (0%)
Pneumonia aspiration	5/3225 (0.2%)
Skin and subcutaneous tissue disorders
Hypersensitivity vasculitis	1/3225 (0%)
Surgical and medical procedures
Coronary angioplasty	1/3225 (0%)
Enterostomy	1/3225 (0%)
Vascular disorders
Aortic aneurysm rupture	3/3225 (0.1%)
Aortic dissection	1/3225 (0%)
Hypotension	1/3225 (0%)
Aortic rupture	1/3225 (0%)
Other (Not Including Serious) Adverse Events
	Lansoprazole 15 mg
	Affected / at Risk (%)	# Events
Total	0/3255 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.