Elsevier

American Heart Journal

Volume 163, Issue 6, June 2012, Pages 931-937.e1
American Heart Journal

Trial Design
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)

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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.

Section snippets

Methods

The RE-ALIGN study is a prospective, randomized, open-label, blinded end-point (PROBE) phase II study comparing dabigatran etexilate with warfarin during a follow-up period of 12 weeks in patients with a mechanical bileaflet heart valve (NCT01452347). The aim of the study is to validate a new dosing regimen based on simulations of PK data from the RE-LY trial,10, 11 for dabigatran etexilate in patients who received a mechanical heart valve.

Discussion

The RE-ALIGN study is the first study to evaluate an alternative to a vitamin K antagonist in patients with a mechanical heart valve. Based on the PK data of dabigatran from the RE-LY study, a dosing algorithm designed to achieve a trough drug level of at least 50 ng/mL will be tested in the study. The patients to be studied in RE-ALIGN will be significantly younger than those in the RE-LY study, and hence, their renal function will be better. Therefore, higher doses of dabigatran etexilate may

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  • Cited by (0)

    Blase A. Canabello, MD served as guest editor for this article.

    RCT reg no. NCT01452347.

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