PRAXBIND®
Efficacy
IN RE-VERSE AD™, PRAXBIND® REVERSED THE ANTICOAGULANT EFFECT OF PRADAXA® IN EMERGENCY SITUATIONS1
RE-VERSE AD™ Trial: A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran
Methods1
- Study Design: Multicenter, prospective, open-label study
- Patients: Final study analysis included 503* patients taking dabigatran who were administered PRAXBIND®. The patients were divided into two groups:
‒ Group A (n=301): Patients who presented with life-threatening or uncontrolled bleeding
‒ Group B (n=202): Patients who required emergency surgery or urgent procedures
- Study Treatment: All patients were to receive 5 g of intravenous PRAXBIND® which was administered as two 50-mL bolus infusions, each containing 2.5 g of PRAXBIND®, no more than 15 minutes apart.
- Primary Endpoint: To determine the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours of administration of PRAXBIND®, based on central laboratory determination of diluted thrombin time (dTT) or ecarin clotting time (ECT) in patients who presented with PRADAXA® (dabigatran etexilate)-related life threatening or uncontrolled bleeding (group A) or who required emergency surgery or urgent procedures (group B)
‒ Reversal was evaluable only for those patients showing prolonged coagulation times prior to idarucizumab treatment2
Results
REVERSAL OF CLOTTING TIME1†‡
Prolongation in the RE-VERSE AD Finalized Analysis: ECT
Reversal of anticoagulation after idarucizumab administration shown as ecarin clotting time (ECT), group A (n=293), group B (n=194) Idarucizumab was administered as two vials of 2.5 g, with no more than 15 minutes apart. Reversal was evident seconds after administration.
In a limited number of patients, elevation of coagulation parameters was observed between 12 and 24 hours after administration of 5 g PRAXBIND®1
REVERSAL OF CLOTTING TIME1†‡
Prolongation in the RE-VERSE AD Finalized Analysis: aPTT
The activated partial-thromboplastin time in the 486 patients in groups A and B who could be assessed. Idarucizumab was administered as two vials of 2.5 g, with no more than 15 minutes apart. More than 98% of patients achieved complete reversal after the administration.
Key findings1,2
- Rapid: PRAXBIND® rapidly reversed the anticoagulant effect of dabigatran in emergency situations.1
- Complete: Median maximum reversal in evaluable patients was 100% in the first 4 hours (primary endpoint; n=503).§1 Most patients achieved complete reversal as measured by ECT (82.2%), or dTT (98.7%).2
Additional findings1
- Cessation of bleeding: 134 (n=203, 67.7%) of the non-ICH patients who had uncontrolled bleeding had confirmed bleeding cessation within 24 hours, with a median time of 2.5 hours.¶
- Clotting: Among the patients who underwent emergency surgery or urgent procedures (n=197), periprocedural hemostasis was assessed as normal in 93.4% (n=184) of patients, mild abnormal in 5.1% (n=10), and moderately abnormal in 1.5% (n=3).
Footnotes:
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*Median age was 78 years and median creatinine clearance (CrCl) was 53 mL/min. Approximately 62% of patients in Group A and 62% of patients in Group B had been treated
with dabigatran 110 mg BID. -
†Determined by mean clotting time below the ULN as measured by ECT and aPTT.
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‡Blood samples were obtained at baseline, after the first infusion, at 10-30 min after the second infusion, and at 1, 2, 4, 12, and 24 hours.4
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§Based on determination for dTT or ECT.
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¶The time to the cessation of bleeding could not be assessed in the 98 patients with intracranial bleeding, because there is dissociation between the clinical course and the
extent of bleeding. -
aPTT, activated partial thromboplastin time; BID, twice daily; CrCl, creatinine clearance; dTT, diluted thrombin time; ECT, ecarin clotting time; ICH, Intracerebral hemorrhage;
ULN, upper limits of normal.
References:
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Pollack CV Jr, et al. N Engl J Med. 2017;377(5):431-441; 1-13 [suppl appendix]
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PRAXBIND® approved package insert. Updated in May 2019 and approved in November 2019.