Dabigatran etexilate in patients with mechanical heart valves

Phase 1

• Conditions: anticoagulation following mechanical heart valve surgery; MedDRA version: 14.0Level: LLTClassification code 10053349Term: Pharmacokinetic studySystem Organ Class: 10022891 - Investigations; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-022685-27-NO
• Lead Sponsor: Boehringer Ingelheim Norway KS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-08-08
• Study Completion: 2013-06-03
• Last Update Posted: 10 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 405

Inclusion Criteria

Patients aged 18 -75 years, either undergoing implantation of a mechanical valve during the current hospital stay or having undergone implantation more than three months prior to randomisation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

1. Patients who have undergone prior valve surgery with implantation of a bioprosthetic or mechanical valve before the index valve replacement surgery.
2. Patients undergoing aortic root replacement and/or replacement of the ascending aorta prior or at index valve replacement surgery..
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.
5. Clinically relevant paravalvular leak related to index valve replacement surgery.
6. Active infective endocarditis.
7. Complex congenital heart abnormality.
8. Acute coronary syndrome within 1 month prior to randomisation.
9. Uncontrolled hypertension
10 Emergency surgery or major trauma within three months of randomisation
11. Planned surgery or intervention within one month post randomisation.
12. Any history of haemorrhagic stroke
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 haemorrhage 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, haemophilia A or B or other hereditary 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 <100 x 10e9/L) at screening
17. Renal impairment (estimated CrCl calculated by Cockcroft-Gault equation) <40mL/min at screening.
18.Liver disease as indicated by at least one of the following:
• Prior and persistent ALT or AST or alkaline phosphatase >3 X upper limit of normal (ULN)
• Active hepatitis C (as evidenced by positive hepatitis C virus ribonucleic acid assay by sensitive polymerase chain reaction (PCR) based assay, such as Roche Monitor or Bayer TMA assay)
• Active hepatitis B (HBs antigen + or anti HBc IgM+)
• 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 pre-existing 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 be allowed to participate in this trial.
21. Patients with a known allergy to dabigatran etexilate or warfarin or their excipients used for the capsule of the drug.
22. Pre-menopausal (last menstruation =1 year prior to screening) who:
•Are pregnant or breast feeding or
•Are not surgically sterile or
•Are of child bearing potential and not practising an acceptable method of birth control, or do not plan to continue practising an acceptable method of birth control throughout the trial (highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
23. Patients weighing less than 40kg.
24. Patients who

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To validate the dosing algorithm for dabigatran etexilate in patients receiving a mechanical heart valve. ;Secondary Objective: Clinical safety and efficacy outcome variables, mortality and morbidity endpoints, will all be evaluated in an exploratory manner;Primary end point(s): The comparison of observed total dabigatran plasma concentrations values at trough compared to values estimated by dose modelling;Timepoint(s) of evaluation of this end point: Day 4-7 following start of dabigatran etexilate; four and twelve weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): clinical efficacy and safety outcome variables will be studies in an exploratory manner;Timepoint(s) of evaluation of this end point: full trial duration (12 weeks)