A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN).
BACKGROUND
Vitamin K antagonists are the only oral anticoagulants approved for long-term treatment of patients with a cardiac valve replacement.


OBJECTIVE
This study aims to test a new dosing regimen for dabigatran etexilate in patients with a mechanical bileaflet valve.


METHODS
Patients aged ≥ 18 years and ≤ 75 years, either undergoing implantation of a mechanical bileaflet valve (aortic or mitral or both) during the current hospital stay or having undergone implantation a mitral bileaflet valve >3 months before randomization, will be randomized between dabigatran etexilate or warfarin (in a ratio of 2:1) in an open-label design. Initial doses of dabigatran will be based on the estimated creatinine clearance, and the doses will be adjusted based on measuring trough dabigatran plasma levels to achieve levels ≥ 50 ng/mL at steady state. Doses will range between 150 mg twice a day and 300 mg twice a day. Warfarin management and target international normalized ratio will be according to current practice guidelines at the discretion of the treating physicians. The plan is to treat 270 patients with dabigatran etexilate for a total study population of approximately 405 patients. Clinical efficacy and safety outcomes will be analyzed in an exploratory manner.


CONCLUSIONS
RE-ALIGN is the first study to test an alternative to warfarin in patients with mechanical heart valves. A definitive phase III study will be planned based on the results of this study.
University Hospitals Leuven, Department of Cardiovascular Medicine, Leuven, Belgium. Frans.VandeWerf@med.kuleuven.be
Frans
F
Van de Werf
Martina
M
Brueckmann
Stuart J
SJ
Connolly
Jeffrey
J
Friedman
Christopher B
CB
Granger
Sebastian
S
Härtter
Ruth
R
Harper
Arie Pieter
AP
Kappetein
Thorsten
T
Lehr
Michael J
MJ
Mack
Herbert
H
Noack
John W
JW
Eikelboom
D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D058833:Antithrombin Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012107:Research Design; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D055815:Young Adult
D000925:Anticoagulants; D058833:Antithrombin Proteins; D001562:Benzimidazoles; D011725:Pyridines; D014859:Warfarin; D000069604:Dabigatran