Photo courtesy of Boehringer Ingelheim
Dabigatran (Pradaxa)
The US Food and Drug Administration (FDA) has granted full approval to idarucizumab (Praxbind®), the specific reversal agent for dabigatran etexilate mesylate (Pradaxa®).
Idarucizumab received accelerated approval from the FDA in October 2015.
Now, the drug has full approval for use in reversing dabigatran’s anticoagulant effects in patients who require emergency surgery/urgent procedures and those who experience life-threatening or uncontrolled bleeding.
When the FDA granted idarucizumab accelerated approval, continued approval of the drug was contingent upon results from the phase 3 RE-VERSE AD™ trial.
Final results from RE-VERSE AD were published in NEJM in July 2017.
The trial enrolled 503 patients who required dabigatran reversal. They were divided into 2 groups:
- Group A included 301 patients with uncontrolled or life-threatening bleeding complications (eg, intracranial hemorrhage or severe trauma after a car accident)
- Group B included 202 patients requiring an invasive procedure or an emergency surgery or intervention (eg, surgery for an open fracture after a fall).
The study’s primary endpoint was the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within 4 hours. The median maximum percentage reversal was 100%, as assessed on the basis of either the diluted thrombin time or the ecarin clotting time.
In group A, 68% of evaluable patients (134/203) had confirmed bleeding cessation within 24 hours of idarucizumab administration. Their median time to hemostasis after idarucizumab administration was 2.5 hours. (The time to the cessation of bleeding could not be assessed in 98 patients with intracranial bleeding.)
For patients in group B, their required procedures began a median of 1.6 hours from idarucizumab administration. Hemostasis during the procedure was described as normal for 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%.
At 90 days, thrombotic events had occurred in 6.3% of patients in group A and 7.4% of those in group B. The 90-day mortality rates were 18.8% and 18.9%, respectively.