Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists

Study Overview
=================
Brief Summary
-----------------
Patients treated with Vitamin K antagonists (VKA) or direct oral anticoagulants as Rivaroxaban, Apixaban, Edoxaban or Dabigatran, who experience severe bleeding and/or need urgent interventions/operations that cannot wait are included in this registry, or during emergency operations.

Detailed Description
-----------------
The Registry will offer the opportunity to evaluate the effects of reversal agents as PCC, aPCC, rVIIa, specific antidots in e.g. severe bleeding patients treated with oral anticoagulants. By collecting case reports from several university hospitals and clinics, different treatment strategies in clinical practice will be observed and evaluated, and may serve as a comprehensive information resource for the safe management with DOA, but also with the long-term anticoagulation based on coumarin derivatives in the near future. The current objective of this registry is to: Document the clinical course and outcome of various clinical bleeding events associated with DOA or VKA in patients with severe life-threatening bleeding making intervention necessary Document the clinical course and outcome of urgent surgical interventions within 24 hours after admission in patients under DOA or VKA treatment. Characterisation of therapeutic strategies in stopping acute life-threatening bleeding including following agents and methods: blood transfusion, platelet concentrates reversal agents [e.g. vitamin K, prothrombin complex concentrate (PCC), activated PCC (aPCC), activated factor VII (aVII), fibrinogen concentrate, fresh frozen plasma (FFP)] specific antidots, e.g. idarucizumab haemodialysis desmopressin tranexamic acid no specific treatment in respect to the above mentioned treatments (e.g. stop of medication and waiting until anticoagulant effect of DOA is decreased).

Official Title
-----------------
Prospective, Observational, Non-interventional Open-label Multicenter Registry Regarding the Management of Severe Bleeding and/or Urgent Interventions During Treatment With Direct Oral Anticoagulants or Vitamin K Antagonists

Conditions
-----------------
Severe Bleeding, Urgent Surgery

Participation Criteria
=================
Eligibility Criteria
-----------------
Patient Eligibility a) Bleeding patients: Anticoagulated patients with DOA or VKA with clinically overt major bleeding according to a specified ISTH definition for non-surgical patients: Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome Bleeding causing a fall in hemoglobin level of 2 g L-1 (1.24 mmol L-1 ) or more leading to transfusion of two or more units of whole blood or red cells. OR b) Acute surgical need Patients treated with DOA or VKA and who need urgent operation which cannot wait (< 24 h after last intake of drug) AND with or without reversal agent use (e.g. PCC, aPCC, rVIIa) (and/or haemodialysis for dabigatran) AND provides informed consent after the acute event

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DOA<br>Expected number of patients estimated by study duration N= 90 patients treated with direct oral anticoagulants (DOA) with acute bleeding N= 40 patients treated with direct oral anticoagulants (DOA) with urgent surgical intervention | |
| VKA<br>Expected number of patients estimated by study duration N= 90 treated with vitamin K antagonists (VKA) with acute bleeding N= 40 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome | Primary observation points (for all patients): In hospital mortality up to 30 days after admission Secondary observation points (group of patients with life threatening bleeding under oral anticoagulation) Stop of bleeding defined according to the treating physicians Fatality rate caused by unstoppable bleeding Use versus no use of reversal agents - difference in outcome? Definition of supportive measures being effective in stopping bleeding Effectiveness of specific antidots Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding Causality assessment: Relation of SAE to anticoagulant medication | open | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome | Secondary observation points (group of patients with acute surgery under oral anticoagulation) Blood loss, number of transfusions necessary Satisfaction of surgeon during and after surgery concerning bleeding Use versus no use of reversal agents - difference in blood loss and number of transfusions? Use versus no use of reversal agents - difference in satisfaction of surgeon using a standardized questionnaire Causality assessment: Relation of SAE to anticoagulant medication Delay in performance of surgery due to anticoagulation | open | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
severe bleeding, dabigatran, rivaroxaban, apixaban, edoxaban, PCC, aPCC, rVIIa, hemodialysis, antidots, idarucizumab