anticoagulant therapy in mechanical heart valves
Conditions
Interventions
Eligible patients, who successfully complete the screening phase and fulfil the
inclusion and exclusion criteria, may be randomised. Patients will be randomly
assigned to either dabigatran etexilate
INR should
be monitored daily for the first four days. Thereafter, measurements should be
every two weeks over the first 3 months after surgery.
Study Population A patients randomised to warfarin ca
Sponsors
Boehringer Ingelheim
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male and female patients aged >= 18 years and
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the total dabigatran concentration at trough. There are no primary or formal secondary efficacy and safety variables. Clinical efficacy outcome variables, mortality and morbidity enpoints will be evaluated in an exploratory manner. The same goes for safety outcome variables. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following mortality/morbidity clinical endpoints will be examined in an exploratory manner: • Bleeding events: major, clinically relevant non major, minor and total (major plus minor) during study treatment as defined by ISTH and by Valve Academic Research Consortium (VARC) [R11-0058] • Heart valve functionality and thrombosis evaluation from clinical routine echocardiography (TTE and/or TEE) and Doppler imaging. TEE should be conducted if there is a clinical suspicion of valve thrombus or valve dysfunction • Incidence of stroke (including haemorrhagic), SSE and valve thrombosis during study treatment • Composite of stroke (including haemorrhagic), SSE, valve thrombosis and major bleedings during study treatment • Composite of stroke (including haemorrhagic), SSE, valve thrombosis, all death • Individual occurrence of ischaemic stroke (fatal and non-fatal), disabling stroke (modified Rankin score >=3), haemorrhagic stroke, SSE, pulmonary embolism, valve thrombosis, MI, TIAs, vascular death (including deaths from bleeding), all deaths and hospitalisations • Incidence of re-operation for mechanical heart valve, para-valvular leakage and endocarditis (per site, per country and overall) • Net clinical benefit (NCB) as defined by disabling strokes (modified Rankin score >3), life threatening bleeding, vascular death, valve thrombosis and MI. The main safety endpoint is the composite of major plus CRNMBEs while on treatment. MBE for the composite primary endpoint will be defined by the ISTH bleeding classification. On-treatment will be defined as the time interval from date of randomisation to date of last randomised medication intake plus six days.Additional safety endpoints are total bleeding events (composite of major plus minor bleedings) . | — |
Countries
Netherlands
Outcome results
None listed