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Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists (RADOA). Focus on New Antidots

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ClinicalTrials.gov Identifier: NCT03537521
Recruitment Status : Withdrawn (due to corona pandemic crisis)
First Posted : May 25, 2018
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
Cardioangiologisches Centrum Bethanien

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 Intervention/treatment
Severe Bleeding Urgent Surgery Procedure: Urgent surgery which can not be postponed to the next 24 hrs

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).

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Study Type : Observational [Patient Registry]
Actual Enrollment : 0 participants
Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration: 30 Days
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
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
DOA
N= 130 patients treated with direct oral anticoagulants (DOAC) with acute bleeding N= 65 patients treated with direct oral anticoagulants (DOAC) with urgent surgical intervention
Procedure: Urgent surgery which can not be postponed to the next 24 hrs
The urgent surgical intervention is not part of the registry protocol. The intervention is the acute event that leads to enrollment in the registry. It might be e.g. the surgical treatment of a trauma, fall, acute abdomen, appendicitis or anything else.

VKA
N= 130 patients treated with vitamin K antagonists (VKA) with acute bleeding N= 65 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention
Procedure: Urgent surgery which can not be postponed to the next 24 hrs
The urgent surgical intervention is not part of the registry protocol. The intervention is the acute event that leads to enrollment in the registry. It might be e.g. the surgical treatment of a trauma, fall, acute abdomen, appendicitis or anything else.




Primary Outcome Measures :
  1. In hospital mortality up to 30 days after admission [ Time Frame: up to 30 days after hospital admission ]
    Death rate (number of deaths)


Secondary Outcome Measures :
  1. Stop of bleeding defined according to the treating physicians [ Time Frame: up to 30 days after hospital admission ]
    Decission according to the treating physicians

  2. Fatality rate caused by unstoppable bleeding [ Time Frame: up to 30 days after hospital admission ]
    Death rate (number of deaths)

  3. Use versus no use of reversal agents - difference in outcome? [ Time Frame: up to 30 days after hospital admission ]
    documentation of use of reversal agents in eCRF

  4. Definition of supportive measures being effective in stopping bleeding [ Time Frame: up to 30 days after hospital admission ]
    documentation of supportive measures in eCRF

  5. Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding [ Time Frame: up to 30 days after hospital admission ]
    time frame until stop of bleeding

  6. Causality assessment: Relation of SAE to anticoagulant medication [ Time Frame: up to 30 days after hospital admission ]
    Decission according to the treating physicians

  7. Blood loss, number of transfusions necessary [ Time Frame: up to 30 days after hospital admission ]
    documentation of supportive measures in eCRF

  8. Satisfaction of surgeon during and after surgery concerning bleeding [ Time Frame: up to 30 days after hospital admission ]
    Decission according to the treating physicians

  9. Use versus no use of reversal agents - difference in blood loss and number of transfusions [ Time Frame: up to 30 days after hospital admission ]
    documentation of supportive measures in eCRF

  10. Delay in performance of surgery due to anticoagulation [ Time Frame: up to 30 days after hospital admission ]
    time Frame documented in eCRF


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.


Information from the National Library of Medicine

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

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

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): NCT03537521


Sponsors and Collaborators
Cardioangiologisches Centrum Bethanien
Investigators
Layout table for investigator information
Principal Investigator: Edelgard Lindhoff-Last, Prof. CCB Studienzentrum GmbH
Additional Information:

Publications:
Lindhoff-Last E, Herrmann E, Lindau S, et al.: Severe hemorrhage associated with oral anticoagulants- a prospective observational study of the clinical course during treatment with vitamin K antagonists or direct oral anticoagulants. Dtsch Arztebl Int 2020; 117: 312-9. DOI: 10.3238/arztebl.2020.0312

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Responsible Party: Cardioangiologisches Centrum Bethanien
ClinicalTrials.gov Identifier: NCT03537521    
Other Study ID Numbers: RADOA.DOT
First Posted: May 25, 2018    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cardioangiologisches Centrum Bethanien:
severe bleeding
dabigatran
rivaroxaban
apixaban
edoxaban
PCC
aPCC
rVIIa
hemodialysis
antidots
idarucizumab
urgent surgery
andexanet alpha
Additional relevant MeSH terms:
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Hemorrhage
Pathologic Processes