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

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ClinicalTrials.gov Identifier: NCT01722786
Recruitment Status : Recruiting
First Posted : November 7, 2012
Last Update Posted : December 1, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease
Severe Bleeding Urgent Surgery

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 Design

Study Type : Observational
Estimated Enrollment : 260 participants
Observational Model: Cohort
Time Perspective: Prospective
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 Start Date : April 2014
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Menadione
U.S. FDA Resources

Groups and Cohorts

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



Outcome Measures

Primary Outcome Measures :
  1. Primary Outcome [ Time Frame: open ]

    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)

    1. Stop of bleeding defined according to the treating physicians
    2. Fatality rate caused by unstoppable bleeding
    3. Use versus no use of reversal agents - difference in outcome?
    4. Definition of supportive measures being effective in stopping bleeding
    5. Effectiveness of specific antidots
    6. Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding
    7. Causality assessment: Relation of SAE to anticoagulant medication


Secondary Outcome Measures :
  1. Secondary Outcome [ Time Frame: open ]

    Secondary observation points (group of patients with acute surgery under oral anticoagulation)

    1. Blood loss, number of transfusions necessary
    2. Satisfaction of surgeon during and after surgery concerning bleeding
    3. Use versus no use of reversal agents - difference in blood loss and number of transfusions?
    4. Use versus no use of reversal agents - difference in satisfaction of surgeon using a standardized questionnaire
    5. Causality assessment: Relation of SAE to anticoagulant medication
    6. Delay in performance of surgery due to anticoagulation


Biospecimen Retention:   Samples Without DNA
If possible, left-over from plasma samples ("retention sample") should be used to perform further analyses as drug concentrations. Retention samples of very low volume would suffice for HPLC (information on collection method needed) to assess plasma concentrations of anticoagulants in these patients.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01722786


Contacts
Contact: Edelgard Lindhoff-Last, Prof. +49-699450280 e.lindhoff-last@ccb.de

Locations
Germany
Cardioangiology Center Bethanien (CCB) Recruiting
Frankfurt am Main, Germany, 60389
Contact: Edelgard Lindhoff-Last, Prof.MD    +49 69 9450280    e.lindhoff-last@ccb.de   
Principal Investigator: Edelgard Lindhoff-Last, Prof         
Sponsors and Collaborators
Cardioangiologisches Centrum Bethanien
Johannes Gutenberg University Mainz
University Hospital Greifswald
University Hospital Dresden
University Hospital, Aachen
University Hospital, Frankfurt
University of Schleswig-Holstein
Vivantes Netzwerk für Gesundheit GmbH
Ruhr University of Bochum
Technische Universität Dresden
Städtisches Klinikum Dresden-Friedrichstadt
More Information

Responsible Party: Prof. Dr. med. E. Lindhoff-Last, M.D., Cardioangiologisches Centrum Bethanien
ClinicalTrials.gov Identifier: NCT01722786     History of Changes
Other Study ID Numbers: RADOA-Registry
First Posted: November 7, 2012    Key Record Dates
Last Update Posted: December 1, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Prof. Dr. med. E. Lindhoff-Last, Cardioangiologisches Centrum Bethanien:
severe bleeding
dabigatran
rivaroxaban
apixaban
edoxaban
PCC
aPCC
rVIIa
hemodialysis
antidots
idarucizumab

Additional relevant MeSH terms:
Hemorrhage
Pathologic Processes
Vitamins
Vitamin K
Anticoagulants
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants