Clinical trial NCT03537521: Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists (RADOA). Focus on New Antidots
Official title: 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
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Severe Bleeding
Urgent Surgery
Keywords: severe bleeding
dabigatran
rivaroxaban
apixaban
edoxaban
PCC
aPCC
rVIIa
hemodialysis
antidots
idarucizumab
urgent surgery
andexanet alpha
Lead sponsor: Cardioangiologisches Centrum Bethanien
Sponsor class: OTHER
First posted: 2018-05-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Expected number of patients estimated by study duration

N= 130 patients treated with direct oral anticoagulants (DOA) with acute bleeding N= 130 treated with vitamin K antagonists (VKA) with acute bleeding

N= 65 patients treated with direct oral anticoagulants (DOA) with urgent surgical intervention N= 65 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention

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 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:

1. 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
2. Document the clinical course and outcome of urgent surgical interventions within 24 hours after admission in patients under DOA or VKA treatment.
3. Characterisation of therapeutic strategies in stopping acute life-threatening bleeding including following agents and methods:

   1. blood transfusion,
   2. platelet concentrates
   3. reversal agents \[e.g. vitamin K, prothrombin complex concentrate (PCC), activated PCC (aPCC), activated factor VII (aVII), fibrinogen concentrate, fresh frozen plasma (FFP)\]
   4. specific antidots, e.g. idarucizumab, Andexanet alpha
   5. haemodialysis
   6. desmopressin
   7. tranexamic acid
   8. no specific treatment in respect to the above mentioned treatments (e.g. stop of medication and waiting until anticoagulant effect of DOA is decreased).

Eligibility criteria: 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

Primary outcomes:
measure: In hospital mortality up to 30 days after admission
timeFrame: up to 30 days after hospital admission
Secondary outcomes:
measure: Stop of bleeding defined according to the treating physicians
timeFrame: up to 30 days after hospital admission
measure: Fatality rate caused by unstoppable bleeding
timeFrame: up to 30 days after hospital admission
measure: Use versus no use of reversal agents - difference in outcome?
timeFrame: up to 30 days after hospital admission
measure: Definition of supportive measures being effective in stopping bleeding
timeFrame: up to 30 days after hospital admission
measure: Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding
timeFrame: up to 30 days after hospital admission
measure: Causality assessment: Relation of SAE to anticoagulant medication
timeFrame: up to 30 days after hospital admission
measure: Blood loss, number of transfusions necessary
timeFrame: up to 30 days after hospital admission
measure: Satisfaction of surgeon during and after surgery concerning bleeding
timeFrame: up to 30 days after hospital admission
measure: Use versus no use of reversal agents - difference in blood loss and number of transfusions
timeFrame: up to 30 days after hospital admission
measure: Delay in performance of surgery due to anticoagulation
timeFrame: up to 30 days after hospital admission
Other outcomes:
Locations:
Study officials:
affiliation: CCB Studienzentrum GmbH
name: Edelgard Lindhoff-Last, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lindhoff-Last E, Herrmann E, Lindau S, Konstantinides S, Grottke O, Nowak-Goettl U, Lucks J, Zydek B, Heymann CV, Birschmann I, Sumnig A, Beyer-Westendorf J, Schellong S, Meybohm P, Greinacher A. Severe Hemorrhage Associated With Oral Anticoagulants. Dtsch Arztebl Int. 2020 May 1;117(18):312-319. doi: 10.3238/arztebl.2020.0312.