麻豆传媒

Idarucizumab restored clotting in most patients on the new oral anticoagulant (NOAC) dabigatran (Pradaxa) who had serious bleeding or required urgent surgery, according to interim results of the phase III

The median maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours of administration was 100%, based on central laboratory analysis of dilute thrombin time or ecarin clotting time.

"Idarucizumab normalized the test results in 88% to 98% of the patients, an effect that was evident within minutes," , of the Pennsylvania Hospital in Philadelphia, and colleagues found.

The study results were reported online in the New England Journal of Medicine in conjunction with a presentation at the International Society on Thrombosis and Haemostasis meeting in Toronto.

In the trial, hemostasis was restored at a median 11.4 hours among 35 of 51 patients with serious bleeding who could be assessed, as determined by local investigators. All patients in the trial received a single 5-g dose of idarucizumab.

For the 36 patients in the trial who underwent a procedure, 33 were reported to have normal intraoperative hemostasis. Two had mildly abnormal hemostasis, and one had moderately abnormal hemostasis.

One thrombotic event occurred within 72 hours after idarucizumab administration in a patient who hadn't restarted anticoagulants.

"The data are convincing that the antidote effectively and immediately neutralized the activity of dabigatran with a satisfactory safety profile," stated, of Beth Israel Deaconess Medical Center in Boston, in an editorial accompanying the paper.

However, "without a control group, it is difficult to assess the clinical benefit that is conferred by the administration of idarucizumab in patients with dabigatran-related bleeding," he cautioned.

Although Bauer called the lack of a control group in the observational study appropriate -- given the lack of established reversal strategies for direct oral anticoagulants -- of the University of North Carolina at Chapel Hill and its education program, wasn't convinced.

"They could have done a design of idarucizumab versus best clinical care, which in many institutions at this point is a prothrombin complex concentrate or recombinant factor VIIa," Moll said in an email to 麻豆传媒, "and they could have looked at clinical outcomes (as primary endpoints) and lab outcomes (as secondary outcomes).

That would have made the study much more complex and expensive. But it would not have been 'unethical.'"

No studies comparing idarucizumab with either placebo or any standard of usual care are planned, Pollack said in an email to 麻豆传媒 through a media relations representative for trial sponsor, Boehringer Ingelheim.

"The clinical situation of the patients enrolled in this study may differ considerably, depending on the reason for their emergent need for reversal," he wrote. "As a result, their clinical outcomes may likewise vary considerably and cannot constitute a consistent primary study endpoint."

Even with the lack of data on actual clinical benefit on bleeding outcomes, Moll called the findings good news.

The agent is the first of a number of antidotes in development for the NOACs to reach phase III testing in clinical scenarios and has priority review status from the FDA.

Because idarucizumab is a novel humanized antibody fragment of dabigatran, it will only reverse that drug; other agents are being developed as antidotes to all the NOACS and even broader activity for the older anticoagulants as well.

Full results from RE-VERSE AD are expected after trial completion in 2017.

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