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

Phase 2

Terminated

• Conditions: Primary Disease
• Interventions: Drug: Dabigatran; Drug: Warfarin

• Registration Number: NCT01868243
• Lead Sponsor: Hospital Ana Nery

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2013-05-28
• Study First Submitted QC: 2013-06-03
• Study First Posted: 2013-06-04
• Study Start: 2013-08
• Primary Completion: 2014-09
• Study Completion: 2014-10
• Results First Submitted: 2015-06-24
• Status Verified: 2015-09
• Results First Submitted QC: 2015-09-14
• Last Update Submitted: 2015-09-14
• Results First Posted: 2015-10-09
• Last Update Posted: 2015-10-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

1. Age from 18 to 64 years at entry
2. Patients with mitral and/or aorthic valve bioprosthesis for at least 3 months postoperatively
3. 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
4. Brain computed tomography scan without hemorrhage or findings of acute cerebral infarction on the last 2 days of screening
5. Exclusion of atrial thrombus or valve prosthesis thrombosis by transesophageal echocardiograph on the last 2 days of screening
6. Written, informed consent

Exclusion Criteria

1. Previous hemorrhagic stroke
2. Ischemic stroke in the last 6 months
3. Severe renal impairment (creatinine clearance rates < 30 ml/min)
4. Active liver disease (any etiology)
5. Concomitant use of any antiplatelet (aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, etc)
6. Increased risk of bleeding (congenital or acquired)
7. Uncontrolled hypertension
8. Gastrointestinal hemorrhage within the past year
9. Anemia (hemoglobin level <10 g/dL) or thrombocytopenia (platelet count < 100 × 109/L)
10. Active infective endocarditis
11. Pregnant or lactating women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dabigatran	Dabigatran	Dabigatran 110 mg BID
Warfarin	Warfarin	Warfarin adjusted-dose

Primary Outcome Measures

Name	Time	Method
Intracardiac Thrombus	90 days	The primary endpoint was the detection of intracardiac thrombus in TEE at the end of follow-up (90 days).

Secondary Outcome Measures

Name	Time	Method
Spontaneous Echo Contrast	90 days	Spontaneous Echo Contrast showed in Transesophageal echocardiography

Trial Locations

Locations (1)

Hospital Ana Nery; 🇧🇷 Salvador, Bahia, Brazil