Boehringer Ingelheim phase III study results confirm benefit of Praxbind as reversal agent for Pradaxa patients in emergency situations

The primary endpoint of RE-VERSE AD was reversal of the anticoagulant effect of Pradaxa within four hours as measured by diluted thrombin time (dTT) and ecarin clotting time (ECT), and was observed in 100 percent of patients (95 percent CI, 100-100). Reversal became evident immediately after administration of Praxbind and was maintained for 24 hours in most patients. Reversal was independent of age, sex, kidney function or dabigatran concentration at baseline. A single 5 g dose of Praxbind was sufficient in 98 percent of patients.

The clinical outcomes captured as secondary endpoints provide insights into the clinical relevance of anticoagulation reversal in patients enrolled with acute bleeding (Group A), who could be assessed for time to cessation of bleeding, it took a median of 2.5 hours until the bleeding had stopped; in patients enrolled with a need for urgent surgery or intervention (Group B), the required procedures could be initiated after a median of 1.6 hours. In 93.4 percent of patients requiring procedures, haemostasis during the procedure was described as normal.

“Emergencies or accidents can happen to anyone. Patients with atrial fibrillation on an anticoagulant may feel anxious about how they might be managed in an emergency,” Professor Charles Pollack, lead investigator of RE-VERSE AD, Professor of Emergency Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, USA commented. “RE-VERSE AD has shown that idarucizumab reverses the anticoagulant effect of dabigatran within minutes and provides immediate, complete and sustained reversal of dabigatran, so that treating physicians can fully focus on dealing with the emergency at hand.”

There were no serious adverse safety signals related to Praxbind observed in the study. Patients in this study were elderly, had numerous comorbidities and presented with serious index events such as intracranial hemorrhage, multiple trauma or sepsis. Mortality rates at 90 days were 18.8 percent (Group A) and 18.9 percent (Group B). At 90 days, thrombotic events had occurred in 6.3 percent of Group A patients and 7.4 percent of Group B patients, which is consistent with rates reported after major surgical procedures or hospitalisation for uncontrolled bleeding in patients who had taken a vitamin K antagonist.

“These final data from RE-VERSE AD fully confirm our interim insights,” Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim commented. “The good news for patients and physicians is that Praxbind is already approved in 61 countries and is available in more than 8,200 sites worldwide, where it can be used to treat patients when urgently needed.” 

Praxbind is the first and only approved specific reversal agent for a non-vitamin K antagonist oral anticoagulant currently available. Boehringer Ingelheim continues to study Praxbind in the RE-VECTO programme, which evaluates usage patterns in a clinical practice setting. Expected completion of the RE-VECTO programme is the end of 2018.

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