RE-ALIGN (Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement) addresses current limitations experienced with warfarin and is designed to identify safe and effective dosing regimen of dabigatran for the prevention of valve thrombosis, stroke and systemic embolism in this patient population, prior to further investigation in a larger phase III study.The current approval of dabigatran does not cover the use in patients with mechanical heart valves.
Vitamin K antagonists, such as warfarin, are the current long-term standard for anticoagulation of patients with a cardiac valve replacement. However, there is only limited information available on the long-term risk of thrombotic and haemorrhagic complications associated with this therapy in patients with modern mechanical bileaflet valves. Additionally, in spite of frequent INR monitoring, patients treated with warfarin spend less that 65% of the time within the targeted therapeutic range (TTR), with TTR in the first three months following valve replacement surgery reported to be as low as 48.5%.
“It is vital that patients with mechanical heart valves are provided with anticoagulant therapies that are safe and effective over the long-term. The current treatment with vitamin K antagonists is associated with significant limitations, creating a need for novel options which have fewer interactions and do not require regular monitoring. We are proud to be the first company looking for an alternative option for these patients by investigating Pradaxa in the RE-ALIGN trial,” said Klaus Dugi, corporate senior vice president Medicine, Boehringer Ingelheim.
The RE-ALIGN study, a prospective, randomised, phase II study, evaluates dabigatran in patients with mechanical bileaflet heart valve during a follow-up period of 12 weeks.Based on the results, a sufficiently powered phase III study is planned to investigate efficacy outcomes for dabigatran in this patient population.
“Pradaxa has already been proven to be a safe and efficacious anticoagulant treatment for stroke prevention in patients with atrial fibrillation,” said Frans Van de Werf, Department of Cardiovascular Medicine, University Hospitals Leuven, Belgium. “However, the presence of a mechanical heart valve is a distinct clinical situation requiring different dosing. The aim of the RE-ALIGN study is to identify dosing regimens of Pradaxa that are expected to be safe and effective for the prevention of thromboembolic complications in patients with mechanical heart valves.”
The different dosing regimens that are under investigation for dabigatran in RE-ALIGN are 150mg bid, 220mg bid, and 300mg bid, with the starting dose determined by the individual patient’s creatinine clearance. The study includes patients with recent surgery for implantation of mechanical bileaflet heart valve who have not yet started oral anticoagulation, and patients who had surgery at least three months before randomisation and are currently taking an oral vitamin K antagonist. Patients are randomised to receive either dabigatran or warfarin. After the 12 week study period, patients are given the opportunity to opt-in to continue treatment with dabigatran within the RE-ALIGN extension trial, allowing investigators to collect long-term safety data.
To date, no investigation has been undertaken to determine the efficacy and safety of any novel oral anticoagulant including dabigatran in patients with mechanical heart valves. Until such data are available, the use of dabigatran for the prevention of thromboembolic complications in patients with mechanical heart valves is not recommended nor approved for clinical practice and is restricted to the setting of a randomised clinical trial only.