A Prospective, Open Label Study Evaluating Two Management Strategies on Gastrointestinal Symptoms in Patients Newly on Treatment With Pradaxa for the Prevention of Stroke and Systemic Embolism With Non-valvular Atrial Fibrillation

Boehringer Ingelheim

Status and phase: Completed; Phase 4

Conditions: Atrial Fibrillation

Treatments: Drug: Pradaxa, within 30 minutes after a meal; Drug: Pradaxa (dabigatran etexilate); Drug: pantoprazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT01493557

1160.128

Details and patient eligibility

About

This is a prospective and open label study that aims to enroll approximately 1200 patients with non-valvular atrial fibrillation (NVAF) not previously treated with Pradaxa® and free of gastrointestinal symptoms (GIS) for at least 2 weeks prior to enrolment. Approximately 125 sites in North America will be recruited. Patients who report GIS during the 3 month treatment period will be randomized to one of two management strategies, and data documenting the intensity and duration of the GIS will be collected.

Enrollment: 1,067 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Documented non-valvular atrial fibrillation (NVAF) for whom Pradaxa® (dabigatran etexilate) is indicated per the current local label, but who have not received treatment with Pradaxa® (dabigatran etexilate), or who have not been started on Pradaxa® (dabigatran etexilate) more than 7 days prior to potential enrolment in the study. NVAF may be documented by 12-lead electrocardiogram, rhythm strip, pacemaker/ implantable cardioverter defibrillator (ICD) electrograms or Holter monitoring
2. Male and female patients, age greater than or equal to 18 years at entry
3. Written, informed consent

Exclusion criteria

1. History within 2 weeks of any of the following gastrointestinal (GI) disorders: heartburn, indigestion, gastritis, upper abdominal pain or discomfort, or gastroesophageal reflux requiring the use of proton pump inhibitors, histamine-2 receptor blockers or antacids. Patients with nausea and/or vomiting within the 2 weeks are not excluded if the symptoms were clearly associated with a self-limited acute or febrile illness. Short-term use of PPIs, as prophylaxis, in a hospital setting for the prevention of stress ulcers is acceptable. Calcium carbonate supplements for calcium replacement is not exclusionary (as long as these products are being used as calcium supplementation/replacement and are not being used to treat or relieve GIS.)
2. GI bleeding within one year or any history of symptomatic or endoscopically documented gastroduodenal ulcer or diverticulitis, unless the cause has been permanently eliminated by medical therapy or by surgery(e.g., patients with peptic ulcer disease with endoscopically proven cure after therapy or lower GI bleeding due to diverticulosis cured by segmental colectomy are not excluded.)
3. not applicable
4. Contraindication to pantoprazole or other proton pump inhibitors, e.g. omeprazole, lansoprazole, rabeprazole, atnoprazole, esomeprazole
5. Contraindication to Pradaxa® (dabigatran etexilate) or known hypersensitivity to Pradaxa® (dabigatran etexilate) or its excipients
6. Hemorrhagic disorder, bleeding diathesis or active pathological bleeding
7. Need for anticoagulant treatment for disorders other than atrial fibrillation
8. Current treatment with rifampin
9. Creatinine clearance <15ml/min (in Canada, <30ml/min), or patients on renal replacement therapy (dialysis)
10. Pre-menopausal women (last menstruation less than or equal to 1 year prior to informed consent) who: are nursing or pregnant, or are of child bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study. Acceptable methods of birth control include abstinence, tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral implantable or injectable contraceptives, double barrier method and vasectomized partner.
11. Patients who have received an investigational drug in the past 30 days or are participating in another drug study
12. Patients considered unreliable by the investigator concerning the requirements for follow-up during the study
13. Any condition the investigator believes would not allow safe participation in the study
14. Contraindication in patients with mechanical heart valves. The use of Pradaxa in the setting of other forms of valvular heart disease, including the presence of a bio-prosthetic valve, is not recommended.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,067 participants in 3 patient groups

Pradaxa (dabigaran etexilate)

Other group

Description:

Patients with non valvular atrial fibrillation for whom Pradaxa is indicated in accordance with the current local label, not previously treated with Pradaxa, will be provided 3 months of treatment for the prevention of stroke and systemic embolism. Patients who report gastrointestinal symptoms (GIS) will be randomized to one of two management strategies, and data documenting the intensity and duration of the GIS will be collected.

Treatment:

Drug: Pradaxa (dabigatran etexilate)

Drug: Pradaxa (dabigatran etexilate)

Pradaxa and pantoprazole

Active Comparator group

Description:

Patients that develop gastrointestinal symptoms (GIS) will be randomized 1:1 to either pantoprazole 40 mg q.a.m., p.o., or taking Pradaxa (dabigatran etexilate) within 30 minutes after a meal

Treatment:

Drug: Pradaxa (dabigatran etexilate)

Drug: pantoprazole

Drug: Pradaxa (dabigatran etexilate)

Pradaxa, 30 minutes after a meal

Active Comparator group

Description:

Patients that develop gastrointestinal symptoms (GIS) will be randomized 1:1 to either pantoprazole 40 mg q.a.m., p.o., or taking Pradaxa (dabigatran etexilate) within 30 minutes after a meal

Treatment:

Drug: Pradaxa, within 30 minutes after a meal