RE-VERSE AD: Anticoagulant Effect of Dabigatran Reversed By New Drug

MedicalResearch.com Interview with:
Dr. Charles Pollack Jr., MA, MD, FACEP
Thomas Jefferson University
Clinical Professor of Emergency Medicine
Philadelphia, PA 19107

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Pollack: There are currently no approved specific reversal agents for non–vitamin K antagonist oral anticoagulants. Idarucizumab, an antibody fragment, was developed to specifically reverse the anticoagulant effects of the oral thrombin inhibitor, dabigatran.

RE-VERSE AD is an ongoing, global Phase III patient study initiated in 2014 to investigate idarucizumab in emergency settings in patients taking dabigatran. We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who either presented with serious bleeding (group A) or required an urgent invasive procedure (group B) which could not be delayed by eight hours. We intentionally designed the study with very broad inclusion criteria to reflect the types of patients who would require urgent anticoagulant reversal in real-world emergency settings.

The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. We also diligently collected clinical outcomes as secondary outcomes, being conscious that these may vary considerably due to the heterogeneity of the patients we included in the study.

In our publication in the New England Journal of Medicine, we present the first results from the study, in an interim analysis of the data from the first 90 patients. The data showed that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in 88 to 98% of the patients who had had elevated clotting times at baseline. The reversal effect was evident within minutes. There were no safety concerns related to idarucizumab among the 90 patients involved in this study – including patients who were given idarucizumab on clinical grounds but were later found to have had normal results on clotting tests at baseline. This is consistent with the experience from the more than 200 volunteers who were administered idarucizumab in previous studies.


MedicalResearch: What should clinicians and patients take away from your report?

Dr. Pollack: 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. As observed in earlier research in volunteers, idarucizumab reversed the anticoagulant effect of dabigatran in patients completely within minutes, even in those rare and challenging critical care situations studied in RE-VERSE AD. There were no safety concerns identified. These data demonstrate that use of idarucizumab can enable physicians to focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Pollack: The RE-VERSE AD study is ongoing. The data presented are the results from an interim analysis. We look forward to gaining even more insights about idarucizumab and how it can support emergency management in patients treated with dabigatran during the further course of the study. We are working on a number of sub-analyses based on the data of this interim analysis and will present them at upcoming scientific meetings. And we will of course present final results once the study is completed.

Citation:

Idarucizumab for Dabigatran Reversal

Charles V. Pollack, Jr., M.D., Paul A. Reilly, Ph.D., John Eikelboom, M.B., B.S., Stephan Glund, Ph.D., Peter Verhamme, M.D., Richard A. Bernstein, M.D., Ph.D., Robert Dubiel, Pharm.D., Menno V. Huisman, M.D., Ph.D., Elaine M. Hylek, M.D., Pieter W. Kamphuisen, M.D., Ph.D., Jörg Kreuzer, M.D., Jerrold H. Levy, M.D., Frank W. Sellke, M.D., Joachim Stangier, Ph.D., Thorsten Steiner, M.D., M.M.E., Bushi Wang, Ph.D., Chak-Wah Kam, M.D., and Jeffrey I. Weitz, M.D.

June 22, 2015DOI: 10.1056/NEJMoa1502000