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.
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.
Trial Stopped: because a significant decrease of viable candidates for the study.
- Warfarin (Coumadin®)Drug
Intervention Desc: Warfarin adjusted-dose ARM 1: Kind: Experimental Label: Warfarin Description: Warfarin adjusted-dose
- Dabigatran (Pradaxa)Drug
Intervention Desc: Group 1 - Dabigatran 110 mg (50 patients) ARM 1: Kind: Experimental Label: Dabigatran Description: Dabigatran 110 mg BID
- Rivaroxaban Drug
Intervention Desc: Group 1 - Rivaroxaban 20 mg (50 patients) ARM 1: Kind: Experimental Label: Rivaroxaban Description: Rivaroxaban 20 mg film-coated tablet
- Allocation: Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||The primary efficacy end point was the composite of stroke (ischemic or hemorrhagic) and systemic embolism.||1 year||Yes|
|Secondary||A individual occurrence of stroke, systemic embolism, or death from all causes.||6 months||Yes|
|Primary||Embolic Events||1 year||Yes|
|Primary||Intracardiac Thrombus||90 days||No|
|Secondary||Spontaneous Echo Contrast||90 days||No|
- Hospital Ana Nery Lead