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

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

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.

Study Overview

• Status: Completed
• Conditions: Urgent Surgery; Severe Bleeding

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).

• Study Type: Observational
• Enrollment (Actual): 272

Contacts and Locations

Study Locations

• Germany
  • Frankfurt am Main, Germany, 60389
    • Cardioangiology Center Bethanien (CCB)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
DOA; 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; 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

Collaborators and Investigators

• Sponsor: Cardioangiologisches Centrum Bethanien
• Collaborators: Goethe University; Ruhr University of Bochum; Technische Universität Dresden; University Hospital Schleswig-Holstein; Johannes Gutenberg University Mainz; University Hospital, Aachen; University Hospital Dresden; University Hospital Greifswald; Vivantes Netzwerk für Gesundheit GmbH; Städtisches Klinikum Dresden-Friedrichstadt

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): July 9, 2019

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: November 6, 2012
• First Posted (Estimate): November 7, 2012

Study Record Updates

• Last Update Posted (Actual): July 16, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: hemodialysis; rivaroxaban; apixaban; edoxaban; dabigatran; PCC; severe bleeding; aPCC; rVIIa; antidots; idarucizumab
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: RADOA-Registry

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO