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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Collaborators:
CTH Mainz
Johannes Gutenberg University Mainz
Charité Berlin
Universitätsklinikum Hamburg-Eppendorf
Hannover Medical School
University Hospital Düsseldorf
University Hospital, Bonn
University Hospital Greifswald
University Hospital Dresden
Information provided by (Responsible Party):
Prof. Dr. E. Lindhoff-Last, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01722786
First received: November 5, 2012
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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, when they receive intervention with a reversal agent (e.g. PCC, aPCC; rVIIa and/or hemodialysis (for removal of dabigatran)).


Condition
Severe Bleeding
Urgent Surgery

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Primary Outcome [ Time Frame: open ] [ Designated as safety issue: Yes ]

    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 treated 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 dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding
    6. Causality assessment: Relation of SAE to anticoagulant medication


Secondary Outcome Measures:
  • Secondary Outcome [ Time Frame: open ] [ Designated as safety issue: Yes ]

    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.


Estimated Enrollment: 130
Study Start Date: August 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
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


Detailed Description:

The Registry will offer the opportunity to evaluate the effects of reversal agents as PCC, aPCC, rVIIa 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. haemodialysis
    5. desmopressin
    6. tranexamic acid
    7. 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 20 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01722786

Contacts
Contact: Edelgard Lindhoff-Last, MD +49-6963015096 lindhoff-last@em.uni-frankfurt.de

Locations
Germany
University Hospital Frankfurt Recruiting
Frankfurt am Main, Germany, 60590
Contact: Edelgard Lindhoff-Last, Prof.MD    +49 69 6301 5096    Edelgard.Lindhoff-Last@kgu.de   
Contact: Helen Mani, PhD    +49 69 6301 5096    Helen.Mani@kgu.de   
Principal Investigator: Edelgard Lindhoff-Last, Prof         
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
CTH Mainz
Johannes Gutenberg University Mainz
Charité Berlin
Universitätsklinikum Hamburg-Eppendorf
Hannover Medical School
University Hospital Düsseldorf
University Hospital, Bonn
University Hospital Greifswald
University Hospital Dresden
  More Information

No publications provided

Responsible Party: Prof. Dr. E. Lindhoff-Last, Division of Angiology, Department of Internal Medicine, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01722786     History of Changes
Other Study ID Numbers: RADOA-Registry
Study First Received: November 5, 2012
Last Updated: May 27, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by Johann Wolfgang Goethe University Hospitals:
severe bleeding
dabigatran
rivaroxaban
apixaban
edoxaban
PCC
aPCC
rVIIa
hemodialysis

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

ClinicalTrials.gov processed this record on October 20, 2014