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

Primary Disease Clinical Trial

— DAWA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01868243
• Other study ID #: DAWA2013
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: May 28, 2013
• Last updated: September 14, 2015
• Start date: August 2013
• Est. completion date: October 2014

Study information

• Verified date: September 2015
• Source: Hospital Ana Nery
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: October 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Primary Disease

Intervention

Drug:
• Dabigatran
Group 1 - Dabigatran 110 mg (50 patients)
• Warfarin
Warfarin adjusted-dose

Locations

Country	Name	City	State
Brazil	Hospital Ana Nery	Salvador	Bahia

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Ana Nery

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005 Nov;5(11):685-94. Review. — View Citation

Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. Erratum in: N Engl J Med. 2010 Nov 4;363(19):1877. — View Citation

Heras M, Chesebro JH, Fuster V, Penny WJ, Grill DE, Bailey KR, Danielson GK, Orszulak TA, Pluth JR, Puga FJ, et al. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol. 1995 Apr;25(5):1111-9. — View Citation

Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006 Sep 16;368(9540):1005-11. — View Citation

Sun JC, Davidson MJ, Lamy A, Eikelboom JW. Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends. Lancet. 2009 Aug 15;374(9689):565-76. doi: 10.1016/S0140-6736(09)60780-7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intracardiac Thrombus	The primary endpoint was the detection of intracardiac thrombus in TEE at the end of follow-up (90 days).	90 days	No
Secondary	Spontaneous Echo Contrast	Spontaneous Echo Contrast showed in Transesophageal echocardiography	90 days	No