Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists (RADOA). Focus on New Antidots

Study Overview
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Brief Summary
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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
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The Registry will offer the opportunity to evaluate the effects of reversal agents as PCC, aPCC, rVIIa, specific antidots in patients needing urgent interventions/operations or in 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, Andexanet alpha 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
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Prospective, Observational, Non-interventional Open-Label, International, Multicenter Registry Regarding the Management of Severe Bleeding and/or Urgent Interventions During Treatment With Direct Oral Anticoagulants or Vitamin K Antagonists

Conditions
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Severe Bleeding, Urgent Surgery

Intervention / Treatment
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* Procedure: Urgent surgery which can not be postponed to the next 24 hrs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 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 Group 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) with or without reversal agent use (e.g. PCC, aPCC, rVIIa) (and/or haemodialysis for dabigatran) provides informed consent after the acute event Exclusion Criteria for Group a and b: Conscious patient by him-/ herself or his/ her available legal representative does not agree with inclusion in the registry Age < 18 years Concomitant participation in an interventional trial

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DOA<br>N= 130 patients treated with direct oral anticoagulants (DOAC) with acute bleeding N= 65 patients treated with direct oral anticoagulants (DOAC) with urgent surgical intervention | Procedure: Urgent surgery which can not be postponed to the next 24 hrs<br>* The urgent surgical intervention is not part of the registry protocol. The intervention is the acute event that leads to enrollment in the registry. It might be e.g. the surgical treatment of a trauma, fall, acute abdomen, appendicitis or anything else.<br>|
| VKA<br>N= 130 patients treated with vitamin K antagonists (VKA) with acute bleeding N= 65 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention | Procedure: Urgent surgery which can not be postponed to the next 24 hrs<br>* The urgent surgical intervention is not part of the registry protocol. The intervention is the acute event that leads to enrollment in the registry. It might be e.g. the surgical treatment of a trauma, fall, acute abdomen, appendicitis or anything else.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In hospital mortality up to 30 days after admission | Death rate (number of deaths) | up to 30 days after hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stop of bleeding defined according to the treating physicians | Decission according to the treating physicians | up to 30 days after hospital admission | 
| Fatality rate caused by unstoppable bleeding | Death rate (number of deaths) | up to 30 days after hospital admission | 
| Use versus no use of reversal agents - difference in outcome? | documentation of use of reversal agents in eCRF | up to 30 days after hospital admission | 
| Definition of supportive measures being effective in stopping bleeding | documentation of supportive measures in eCRF | up to 30 days after hospital admission | 
| Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding | time frame until stop of bleeding | up to 30 days after hospital admission | 
| Causality assessment: Relation of SAE to anticoagulant medication | Decission according to the treating physicians | up to 30 days after hospital admission | 
| Blood loss, number of transfusions necessary | documentation of supportive measures in eCRF | up to 30 days after hospital admission | 
| Satisfaction of surgeon during and after surgery concerning bleeding | Decission according to the treating physicians | up to 30 days after hospital admission | 
| Use versus no use of reversal agents - difference in blood loss and number of transfusions | documentation of supportive measures in eCRF | up to 30 days after hospital admission | 
| Delay in performance of surgery due to anticoagulation | time Frame documented in eCRF | up to 30 days after hospital admission | 

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