OREANDA-NEWS. June 24, 2015. RE-VERSE AD™ is an ongoing, global Phase III patient study initiated by Boehringer Ingelheim in 2014 to investigate idarucizumab* in emergency settings.3,10 Up to 300 patients taking dabigatran, aged 18 years or over are expected to be enrolled from more than 400 centres in 38 countries worldwide.3,11 Group A includes patients with uncontrollable or life-threatening bleeding deemed to require reversal, whereas Group B includes patients who needed surgery or an invasive procedure within 8 hours for which normal blood clotting (haemostasis) were required.3

The broad inclusion criteria reflect the types of patients that would require urgent anticoagulant reversal in the real-world emergency setting.1,3 These include severely ill or injured patients, (e.g. patients with sepsis, a severe intracranial haemorrhage or a large vessel injury).1,3 Furthermore, the study investigators are also allowed to administer any other type of therapies for patient management (including other blood products), as demanded by the clinical situation.3

Patients received 5 g of intravenous idarucizumab* administered as two 50 ml bolus infusions, each containing 2.5 g of idarucizumab*, no more than 15 minutes apart.3 Blood was collected and assessed for anticoagulant effect at baseline, after administration of the first vial of idarucizumab*, and then between 10 and 30 minutes and 1,2,4,12 and 24 hours after administration of the second vial.3

The primary endpoint was the maximum degree of reversal of the anticoagulant effect of dabigatran, determined using different laboratory tests (including the coagulations tests diluted thrombin time (dTT) and ecarin clotting time (ECT)) at any point from the end of the first idarucizumab* infusion, up to 4 hours after administration of the second infusion.1,3

Secondary endpoints include the proportion of patients achieving complete normalisation of the dTT or ECT in 4 hours, the reduction in unbound dabigatran concentration, and clinical outcomes as assessed by the treating clinician.1,3 In Group A patients, clinical outcomes included the extent of bleeding, severity of bleeding and haemodynamic stability.1,3 In Group B patients, haemostasis was classified as normal or as mildly, moderately or severely abnormal.1,3 Adverse events were monitored from the time of idarucizumab* infusion to 90 days post-infusion including suspected thrombotic events or deaths (classified as vascular or non-vascular in origin).1,3