TORONTO—Interim results of a phase 3 study suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of
dabigatran in real-world situations.
In the RE-VERSE AD trial, idarucizumab normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
In addition, researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
These results have been published in NEJM and presented at the 2015 ISTH Congress (abstract LB005). The study was sponsored by Boehringer Ingelheim, the company developing idarucizumab and dabigatran.
“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 study investigator Charles Pollack, MD, of the University of Pennsylvania in Philadelphia.
Because RE-VERSE AD was designed to evaluate how idarucizumab would perform in real-world situations, severely ill or injured patients were eligible for enrollment. The interim analysis included data from 90 patients in emergency settings who were taking dabigatran and required reversal.
The patients were divided into 2 groups: those with uncontrolled or life-threatening bleeding complications, such as intracranial hemorrhage or severe trauma (group A, n=51), and patients requiring emergency surgery or an invasive procedure (group B, n=39).
The primary endpoint of the study is the degree to which 5 g of idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.
The researchers were able to evaluate the percentage of reversal by dTT in 68 patients (40 in group A and 28 in group B) and the percentage of reversal by ECT in 81 patients (47 in group A and 34 in group B).
The dTT was normalized in 98% of evaluable patients in group A and 93% in group B. The ECT was normalized in 89% of evaluable patients in group A and 88% in group B.
At 12 hours and 24 hours, the dTT was below the upper limit of the normal range in 90% of evaluable patients in group A and 81% in group B. The ECT was below the upper limit of the normal range in 72% of evaluable group A patients and 54% of evaluable group B patients.
Among the 35 evaluable patients in group A, hemostasis was restored at a median of 11.4 hours. Among the 36 patients in group B who underwent a procedure, 33 had normal intraoperative hemostasis. Two patients had mildly abnormal hemostasis, and 1 patient had moderately abnormal hemostasis.
“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,” Dr Pollack said.
“These data demonstrate that use of idarucizumab can help physicians focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.”
Twenty-one patients (13 in group A and 8 in group B) experienced serious adverse events during the study.
This included 18 events that led to death, 5 thrombotic events, 2 cases of gastrointestinal hemorrhage, a postoperative wound infection, a case of delirium, a case of right ventricular failure, and a case of pulmonary edema. (Some patients had more than one serious adverse event.)
