Primary Disease
Conditions
Keywords
Atrial Fibrillation, Bioprosthesis, Stroke, Dabigatran, Warfarin
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.
Interventions
DRUGDabigatran
Group 1 - Dabigatran 110 mg (50 patients)
DRUGWarfarin
Warfarin adjusted-dose
Sponsors
Hospital Ana Nery
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intracardiac Thrombus | 90 days | The primary endpoint was the detection of intracardiac thrombus in TEE at the end of follow-up (90 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneous Echo Contrast | 90 days | Spontaneous Echo Contrast showed in Transesophageal echocardiography |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Dabigatran 110 mg BID
Dabigatran: Group 1 - Dabigatran 110 mg (50 patients) | 15 |
| Warfarin Warfarin adjusted-dose
Warfarin: Warfarin adjusted-dose | 12 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | Dabigatran | Warfarin | Total |
|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 10 | 46 years STANDARD_DEVIATION 6 | 47 years STANDARD_DEVIATION 8 |
| Region of Enrollment Brazil | 15 participants | 12 participants | 27 participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 15 | 1 / 12 |
| serious Total, serious adverse events | 1 / 15 | 0 / 12 |
Outcome results
Primary
Intracardiac Thrombus
The primary endpoint was the detection of intracardiac thrombus in TEE at the end of follow-up (90 days).
Time frame: 90 days
Population: A total of 34 patients were selected between August 2013 and November 2014 (6 were excluded for previous intracardiac thrombus; 1 for unstable INR control). Of the 27 randomized, 15 were assigned to receive dabigatran and 12 to receive warfarin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Intracardiac Thrombus | 0 participants |
| Warfarin | Intracardiac Thrombus | 1 participants |
Secondary
Spontaneous Echo Contrast
Spontaneous Echo Contrast showed in Transesophageal echocardiography
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran | Spontaneous Echo Contrast | 2 participants |
| Warfarin | Spontaneous Echo Contrast | 1 participants |