Clinical trial NCT01722786: Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Bleeding
Urgent Surgery
Keywords: severe bleeding
dabigatran
rivaroxaban
apixaban
edoxaban
PCC
aPCC
rVIIa
hemodialysis
antidots
idarucizumab
Lead sponsor: Cardioangiologisches Centrum Bethanien
Sponsor class: OTHER
Collaborators: name: Johannes Gutenberg University Mainz
name: University Hospital Greifswald
name: University Hospital Dresden
name: University Hospital, Aachen
name: Goethe University
name: University Hospital Schleswig-Holstein
name: Vivantes Netzwerk für Gesundheit GmbH
name: Ruhr University of Bochum
name: Technische Universität Dresden
name: Städtisches Klinikum Dresden-Friedrichstadt
First posted: 2012-11-07
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Expected number of patients estimated by study duration

N= 90 patients treated with direct oral anticoagulants (DOA) with acute bleeding N= 90 treated with vitamin K antagonists (VKA) with acute bleeding

N= 40 patients treated with direct oral anticoagulants (DOA) with urgent surgical intervention N= 40 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 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:

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
   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: Patient Eligibility

1. 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
2. with or without reversal agent use (e.g. PCC, aPCC, rVIIa) (and/or haemodialysis for dabigatran)

   AND
3. provides informed consent after the acute event

Primary outcomes:
measure: Primary Outcome
timeFrame: open
Secondary outcomes:
measure: Secondary Outcome
timeFrame: open
Other outcomes:
Locations:
city: Frankfurt am Main
country: Germany
facility: Cardioangiology Center Bethanien (CCB)
Study officials:
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.
citation: Pfeilschifter W, Lindhoff-Last E, Alhashim A, Zydek B, Lindau S, Konstantinides S, Grottke O, Nowak-Gottl U, von Heymann C, Birschmann I, Beyer-Westendorf J, Meybohm P, Greinacher A, Herrmann E; RADOA-Registry Investigators (Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists Registry). Intracranial bleeding under vitamin K antagonists or direct oral anticoagulants: results of the RADOA registry. Neurol Res Pract. 2022 May 2;4(1):16. doi: 10.1186/s42466-022-00183-y.