A Randomised, phase II study to Evaluate the sAfety of oraL dabIGatran etexilate in patients after heart valve replacemeNt. (RE-ALIGN)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

1. Male and female patients aged >= 18 years and <= 75 years
2. For study population A - undergone elective implantation of bileaflet mechanical heart valve(s) in the aortic and/or mitral posion during the current hospital stay and not started oral coagulation, or
For study population B - undergone elective implantation of bileaflet mechanical heart valve(s) in the mitral position more than three months prior to randomisation.
Patients (Population A and B) receiving CABG concomitantly with the valve replacement may be included.
3. The patient must be able to give informed consent in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations.

Exclusion Criteria

1. Patients who have undergone prior valve surgery before the index surgery defined for this study.
2.Patients undergoing aortic root surgery and/orreplacement of the ascending aorta at the time of valve replacement.
3. Patients undergoing bioprosthetic or mechanical tricuspid or pulmonary valve replacement
4. Tricuspid valve repair prior or at index valve replacement in a patient with double valve replacement (AVR+MVR)
5.Clinically relevant paravalvular leak related to vavle replacement surgery.
6. Active infective endocarditis.
7. Complex congenital heart abnormality.
8. Acute coronary syndrome within 1 month prior to randomisation.
9. Uncontrolled hypertension (systolic blood pressure (SBP) >180 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg.
10. Emergency surgery or major trauma within three months of randomisation.
11.Planned surgery or intervention within 1 months post randomisation.
12. Any history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV malformation or aneurysm.
13. History of intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding unless the causative factor has been permanently eliminated or repaired (e.g. by surgery).
14. Gastrointestinal (GI) hemorrhage within the past year, unless the cause has been permanently eliminated (e.g. by surgery) or symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days.
15.Haemorrhagic disorder or bleeding diathesis (e.g. von Willebrand disease, hemophilia A or B or other heriditary bleeding disorder, history of spontaneous intra-articular bleeding, history of prolonged bleeding after surgery/intervention).
16. History of thrombocytopenia, including heparin-induced thrombocytopenia or a platelet count <100X10 9/L at screening (visit 1).
17. Renal impairment (estimated CrCl calculated by Cockcroft-Gault equation) < 40mL/min at screening.
18. Liver disease as indicated by one of the following:
• Prior and persistent ALT or AST or AF > 3 X ULN, and/or
• Active hepatitis C (as evidenced by positive hepatitis C virus ribonucleic acid assay by sensitive polymerase chain reaction (PCR) based assay, such as Roch Monitor or Bayer TMA assay) and/or
• Active hepatitis B1 (HBs antigen + or anti HBc IgM+) and/or
• Active hepatitis A
19. Patients who will continue to require treatment with dual antiplatelet therapy.
20. Ongoing or planned treatment with long-term oral anticoagulants for alternative indications during the course of the study (e.g. treatment of VTE, secondary prevention of VTE) with the exception of anticoagulation for stroke prevention in patients with preexisting AF. Patients with prior use of oral anticoagulants for SPAF or for prevention of thromboembolic events due to the presence of a mechanical heart valve will e allowed to participate in this trial.
21. Need for continued treatment with ticlopidine, ticagrelor, prasugrel, systemic ketoconazole, itraconazole, posaconazole, cyclosporine, tacrolimus, dronedarone, rifampicin, carbamazepine, st John's wort or any cytotoxic/myeolosuppressive therapy.
22. Recent malignancy or radiation therapy (<=6 months) unless the malignancy was a basal cell carcinoma that was completely removed.
23. Patients with a known allergy to dabigatran etexilate or to the excipients used for the capsule of the drug.
24. Patients with a kn

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is the total dabigatran concentration at trough. There are<br /><br>no primary or formal secondary efficacy and safety variables. Clinical efficacy<br /><br>outcome variables, mortality and morbidity enpoints will be evaluated in an<br /><br>exploratory manner. The same goes for safety outcome variables.</p><br>

Secondary Outcome Measures