Dabigatran Versus Warfarin After Mitral and/or Aortic Bioprosthesis Replacement and Atrial Fibrillation Postoperatively

Study Overview
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Brief Summary
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DAWA is a phase 2, prospective, open-label, randomized, pilot study. The main variable to be observed in this study is intracardiac thrombus. There are no formal primary or secondary clinical efﬁcacy or safety outcomes because it is a pilot study.

Detailed Description
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Mortality and morbidity events (reversible ischemic neurological deficit, ischemic and hemorrhagic stroke, systemic embolism, any bleeding, prosthesis valve thrombosis and death) were evaluated in an exploratory manner. The details of the trial design have been previously described.8 The trial protocol was approved by the local ethics and research committee in the city of Salvador-Brazil, and written informed consent was obtained from all patients. An independent data and safety monitoring board closely monitored the trial. All the members contributed to the interpretation of the results, wrote the first version of the manuscript and approved all versions, made the decision to submit the manuscript for publication, and vouch for the accuracy and completeness of the data reported and the fidelity of this article to the study protocol. Patients eligible for inclusion in the study were 18 to 64 years old, underwent mitral and/or aortic bioprosthesis valve replacement at least 3 months prior to entering the study and had documented AF postoperatively in addition to exclusion of atrial thrombus or valve prosthesis thrombosis by transesophageal echocardiography (TEE). Non-contrast brain computed tomography (CT) without hemorrhage or findings of acute cerebral infarction on the last 2 days of screening was also necessary. Patients were randomly assigned to receive dabigatran or warfarin by a computer generated list of random numbers performed to 1:1 ratio between the groups. Following that, the allocation sequence was concealed from the researcher enrolling participants in sequentially numbered, opaque, black, sealed envelopes. After randomization, patients had study visits scheduled at 7 days (via telephone) and at 30 days (personally) with a monthly follow-up for 90 days. After this, non-contrast brain CT and TEE were repeated. The former was executed to document possible cerebral events with no clinical expression and the latter to analyze the incidence of intracardiac thrombi, new dense spontaneous echo contrast (SEC) or its resolution, in addition to thrombosis or dysfunction of valvular prosthesis.

Official Title
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Dabigatran Versus Warfarin After Mitral and Aortic Bioprosthesis Replacement for the Management of Atrial Fibrillation Postoperatively: Pilot Study

Conditions
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Primary Disease

Intervention / Treatment
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* Drug: Dabigatran
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 64 years at entry Patients with mitral and/or aorthic valve bioprosthesis for at least 3 months postoperatively There is 12-lead electrocardiogram documented AF on the day of screening or randomization; or a 24-hour Holter electrocardiogram recording showing AF episodes postoperatively Brain computed tomography scan without hemorrhage or findings of acute cerebral infarction on the last 2 days of screening Exclusion of atrial thrombus or valve prosthesis thrombosis by transesophageal echocardiograph on the last 2 days of screening Written, informed consent Exclusion Criteria: Previous hemorrhagic stroke Ischemic stroke in the last 6 months Severe renal impairment (creatinine clearance rates < 30 ml/min) Active liver disease (any etiology) Concomitant use of any antiplatelet (aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, etc) Increased risk of bleeding (congenital or acquired) Uncontrolled hypertension Gastrointestinal hemorrhage within the past year Anemia (hemoglobin level <10 g/dL) or thrombocytopenia (platelet count < 100 × 109/L) Active infective endocarditis Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran<br>Dabigatran 110 mg BID | Drug: Dabigatran<br>* Group 1 - Dabigatran 110 mg (50 patients)<br>* Other names: Pradaxa® (dabigatran etexilate) 110mg twice daily;|
| Active Comparator: Warfarin<br>Warfarin adjusted-dose | Drug: Warfarin<br>* Warfarin adjusted-dose<br>* Other names: Warfarin adjusted-dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracardiac Thrombus | The primary endpoint was the detection of intracardiac thrombus in TEE at the end of follow-up (90 days). | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous Echo Contrast | Spontaneous Echo Contrast showed in Transesophageal echocardiography | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Bioprosthesis, Stroke, Dabigatran, Warfarin