Investigational drug reverses anticoagulant effect of dabigatran in minutes: Study

Use of investigational reversal agent idarucizumab can allow physicians to focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients, according to a study published in the New England Journal of Medicine.

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The data was also presented as a late-breaker at the International Society of Thrombosis and Haemostasis 2015 Congress in Toronto, Canada.

Idarucizumab is currently under review by FDA as a specific reversal agent for the anticoagulant effect of dabigatran in patients needing emergency or urgent surgery or procedures, or for life-threatening or uncontrolled bleeding events.

In an interim analysis of the ongoing global phase 3 RE-VERSE A study showed that 5 g of idarucizumab reversed the anticoagulant effect of dabigatran the active ingredient in Pradaxa (dabigatran etexilate mesylate) in patients requiring urgent anticoagulant reversal within minutes. No safety concerns relating to idarucizumab were identified.

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RE-VERSE AD was designed to evaluate the types of patients and real-world situations healthcare professionals may see in the emergency setting, according to lead study author Charles Pollack, professor of emergency medicine at the Perelman School of Medicine of the University of Pennsylvania School of Medicine in Philadelphia.

In the study, patients were categorized into 2 groups: (A) Patients with uncontrolled or life-threatening bleeding complications, eg, intracranial hemorrhage or severe trauma after a car accident (Group A, n= 51), or (B) Patients requiring emergency surgery or an invasive procedure, eg, surgery for an open fracture after a fall or an incarcerated hernia with ischemic bowel (Group B, n=39). The primary end point of the study is the degree of reversal of the anticoagulant effect of dabigatran achieved by 5 g idarucizumab within 4 hours, as measured by diluted thrombin time (dTT) and ecarin clotting time (ECT).

NEXT: RE-VERSE AD interm analysis

The interim analysis from RE-VERSE AD included data from 90 patients in the emergency setting who were taking dabigatran and required reversal. Of the 81 patients that presented with elevated anticoagulation levels at baseline as measured with ECT, results showed:

• The study met its primary end point, achieving 100% maximum reversal as median value across all patients

• Reversal was evident immediately after administration of the first vial of idarucizumab and was complete in all but 1 patient

• After 4 and 12 hours, laboratory tests showed normal coagulation levels in almost 90% of patients

• Normal blood clotting (haemostasis) during surgery was reported in 92% of the patients that required surgery or invasive procedures

• There was no signal of a pro-coagulant effect following administration of idarucizumab

• Thrombotic events occurred in 5 patients, none of whom was receiving antithrombotic therapy at the time of the event

• There were 18 deaths overall.  Mortality within 96 hours of study enrolment appeared to be related to the original reason for emergency admission to the hospital, while all later events appeared to be related to comorbidities

As observed in earlier research in volunteers, idarucizumab reversed the anticoagulant effect of dabigatran in patients completely within minutes, even in those rare critical care situations studied in RE-VERSE AD. These data demonstrate that use of idarucizumab can allow physicians to focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.

“RE-VERSE AD is the first study to examine a specifically targeted reversal agent in patients actively being treated with a novel anticoagulant,” said lead study author Charles Pollack, professor of emergency medicine at the Perelman School of Medicine of the University of Pennsylvania School of Medicine in Philadelphia. “The interim results show that idarucizumab provides immediate, full, and sustained reversal of dabigatran in patients requiring urgent procedures or with serious bleeding complications.

The interim analysis from RE-VERSE AD is important for healthcare professionals, as it provides the first insights into the effect of a specific reversal agent to a non-vitamin K antagonist oral anticoagulant during real-world emergency situations,” said Dr Pollack.

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