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

Terminated

Phase 2/3 Results

Update History

13 Oct '15
The Summary of Purpose was updated.
New
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.
Old
This randomized open study (pilot study) was designed to compare twice-daily oral Dabigatran with dose-adjusted warfarin for the prevention of stroke (ischemic or hemorrhagic) and systemic embolism in persistent or permanent atrial fibrillation after bioprosthesis replacement.
The description was updated.
New
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.
Old
Between the period of August 2013 to July 2014, 100 patients with chronic rheumatic valve disease undergoing bioprosthetic valve replacement (mitral and/or aortic) in the cardiology service of Hospital Ana Nery in Salvador - Brazil, with persistent or permanent atrial fibrillation postoperatively will be selected to this randomized open pilot study. By a process of simple randomization, half (50 patients) will use for 3 to 6 months of Dabigatran, and other half will use warfarin (the same period). Episodes of ischemic or hemorrhagic stroke, thromboembolism and bleeding (major and minor) will be closely observed.
The eligibility criteria were updated.
New
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
Old
Inclusion Criteria: - Patients between 18 and 64 years, with chronic rheumatic valvular disease after bioprosthesis replacement with permanent or persistent atrial fibrillation will be eligible; Exclusion Criteria: - Previous stroke (ischemic or hemorrhagic) - Severe renal impairment (creatinine clearance rates <30 ml/mn); - active liver disease; - increased risk of bleeding; - uncontrolled hypertension;
A location was updated in Salvador.
New
The overall status was removed for Hospital Ana Nery.
10 Jul '13
A location was updated in Salvador.
New
The overall status was removed for Hospital Ana Nery.
14 Jun '13
Trial acronym was updated.
New
DAWA
Trial name was updated.
New
Dabigatran Versus Warfarin After Mitral and/or Aortic Bioprosthesis Replacement and Atrial Fibrillation Postoperatively
The Summary of Purpose was updated.
New
This randomized open study (pilot study) was designed to compare twice-daily oral Dabigatran with dose-adjusted warfarin for the prevention of stroke (ischemic or hemorrhagic) and systemic embolism in persistent or permanent atrial fibrillation after bioprosthesis replacement.
Old
This randomized open study (pilot study) was designed to compare once-daily oral rivaroxaban with dose-adjusted warfarin for the prevention of stroke (ischemic or hemorragic) and systemic embolism in persistent or permanent atrial fibrillation after bioprosthesis replacement.
The description was updated.
New
Between the period of August 2013 to July 2014, 100 patients with chronic rheumatic valve disease undergoing bioprosthetic valve replacement (mitral and/or aortic) in the cardiology service of Hospital Ana Nery in Salvador - Brazil, with persistent or permanent atrial fibrillation postoperatively will be selected to this randomized open pilot study. By a process of simple randomization, half (50 patients) will use for 3 to 6 months of Dabigatran, and other half will use warfarin (the same period). Episodes of ischemic or hemorrhagic stroke, thromboembolism and bleeding (major and minor) will be closely observed.
Old
Between the period of July 2012 to July 2013, 100 patients with chronic rheumatic valve disease undergoing bioprosthetic valve replacement (mitral and/or aortic) the cardiology service of Hospital Ana Nery in Salvador - Brazil, with persistent or permanent atrial fibrillation postoperatively will be selected to this randomized open pilot study. By a process of simple randomization, half (50 patients) will use for 3 to 6 months of Rivaroxaban, and other half will use warfarin (the same period). Episodes of ischemic or hemorrhagic stroke, thromboembolism and bleeding (major and minor) will be closely observed. Preoperative surgical risk will be quantified with the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and the Society of Thoracic Surgeons 2008 cardiac surgery risk model (the STS model) for isolated valve surgery.
The eligibility criteria were updated.
New
Inclusion Criteria: - Patients between 18 and 64 years, with chronic rheumatic valvular disease after bioprosthesis replacement with permanent or persistent atrial fibrillation will be eligible; Exclusion Criteria: - Previous stroke (ischemic or hemorrhagic) - Severe renal impairment (creatinine clearance rates <30 ml/mn); - active liver disease; - increased risk of bleeding; - uncontrolled hypertension;
Old
Inclusion Criteria: - Patients between 18 and 64 years, with chronic rheumatic valvular disease after bioprosthesis replacement with permanent or persistent atrial fibrilattion will be eligible; Exclusion Criteria: - Previous stroke (ischemic or hemorragic) - Severe renal impairment (creatinine clearance rates <30 ml/mn); - active liver disease;