Clinical Trials

Date: 2017-07-11

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in The New English Journal of Medicine

Company: Boehringer Ingelheim (Germany)

Product: Praxbind® (idarucizumab)

Action mechanism:

• monoclonal antibody. Idarucizumab is a fully humanized antibody fragment, or Fab, being investigated as a specific antidote for Pradaxa®. Pre-clinical studies indicate idarucizumab binds specifically to and inhibits dabigatran with no other expected interactions.
• Praxbind® is the first and only specific non-vitamin K antagonist oral anticoagulant (NOAC) reversal agent approved for use in emergency situations when immediate reversal of the anticoagulant effect of Pradaxa® is required.

Disease: specific antidote for Pradaxa® (dabigatran etexilate) - reversion of the anticoagulant effect of dabigatran due to uncontrolled life-threatening bleeding requiring urgent intervention or a need to undergo an emergency surgery/urgent invasive procedure.

Therapeutic area: Cardiovascular diseases - Cerebrovascular diseases

Country: Chile, Czech Republic, Estonia, Latvia, Lebanon, Slovakia

Trial details:

• RE-VERSE AD™ is a Phase III global study of patients taking dabigatran who require urgent procedures or have uncontrolled bleeding. The study began in May 2014 and investigated a reversal agent for a non-vitamin K antagonist oral anticoagulant (NOAC) in real-world emergency settings. It enrolled a total of 503 patients at 173 sites in 39 countries, which were included in one of two groups:
• - Group A: 301 patients (60 percent) presenting with uncontrolled or life-threatening bleeding (e.g. gastrointestinal [GI] and intracranial [ICH] bleeds)
• - Group B: 202 patients (40 percent) requiring an invasive procedure or an emergency surgery or intervention (e.g. because of a hip fracture). (NCT02104947)

Latest news:

• • On July 11, 2017, Boehringer Ingelheim announced final results from RE-VERSE AD™. The findings were presented at the International Society on Thrombosis and Haemostasis (ISTH) 26th Biennial Congress in Berlin, Germany and simultaneously published in the New England Journal of Medicine.
• The study shows that Praxbind® (idarucizumab) was able to immediately and completely reverse the anticoagulant effect of Pradaxa® (dabigatran etexilate) in patients in emergency situations. The primary endpoint of RE-VERSE AD™ was reversal of the anticoagulant effect of Pradaxa® within four hours as measured by diluted thrombin time (dTT) and ecarin clotting time (ECT), and was observed in 100 percent of patients (95 percent CI, 100-100). Reversal became evident immediately after administration of Praxbind® and was maintained for 24 hours in most patients. Reversal was independent of age, sex, kidney function or dabigatran concentration at baseline. A single 5 g dose of Praxbind® was sufficient in 98 percent of patients.
• The clinical outcomes captured as secondary endpoints provide insights into the clinical relevance of anticoagulation reversal:1,2 in patients enrolled with acute bleeding (Group A), who could be assessed for time to cessation of bleeding, it took a median of 2.5 hours until the bleeding had stopped; in patients enrolled with a need for urgent surgery or intervention (Group B), the required procedures could be initiated after a median of 1.6 hours. In 93.4 percent of patients requiring procedures, haemostasis during the procedure was described as normal.
• There were no serious adverse safety signals related to Praxbind® observed in the study. Patients in this study were elderly, had numerous comorbidities and presented with serious index events such as intracranial hemorrhage, multiple trauma or sepsis. Mortality rates at 90 days were 18.8 percent (Group A) and 18.9 percent (Group B). At 90 days, thrombotic events had occurred in 6.3 percent of Group A patients and 7.4 percent of Group B patients, which is consistent with rates reported after major surgical procedures or hospitalisation for uncontrolled bleeding in patients who had taken a vitamin K antagonist.
• Boehringer Ingelheim continues to study Praxbind® in the RE-VECTO™ programme, which evaluates usage patterns in a clinical practice setting. Expected completion of the RE-VECTO™ programme is the end of 2018.

Is general: Yes