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

Urgent Surgery Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03537521
• Other study ID #: RADOA.DOT
• Status: Withdrawn
• Start date: April 2020
• Est. completion date: April 2023

Study information

• Verified date: July 2020
• Source: Cardioangiologisches Centrum Bethanien
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2023
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Severe Bleeding
• Urgent Surgery

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cardioangiologisches Centrum Bethanien

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In hospital mortality up to 30 days after admission	Death rate (number of deaths)	up to 30 days after hospital admission
Secondary	Stop of bleeding defined according to the treating physicians	Decission according to the treating physicians	up to 30 days after hospital admission
Secondary	Fatality rate caused by unstoppable bleeding	Death rate (number of deaths)	up to 30 days after hospital admission
Secondary	Use versus no use of reversal agents - difference in outcome?	documentation of use of reversal agents in eCRF	up to 30 days after hospital admission
Secondary	Definition of supportive measures being effective in stopping bleeding	documentation of supportive measures in eCRF	up to 30 days after hospital admission
Secondary	Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding	time frame until stop of bleeding	up to 30 days after hospital admission
Secondary	Causality assessment: Relation of SAE to anticoagulant medication	Decission according to the treating physicians	up to 30 days after hospital admission
Secondary	Blood loss, number of transfusions necessary	documentation of supportive measures in eCRF	up to 30 days after hospital admission
Secondary	Satisfaction of surgeon during and after surgery concerning bleeding	Decission according to the treating physicians	up to 30 days after hospital admission
Secondary	Use versus no use of reversal agents - difference in blood loss and number of transfusions	documentation of supportive measures in eCRF	up to 30 days after hospital admission
Secondary	Delay in performance of surgery due to anticoagulation	time Frame documented in eCRF	up to 30 days after hospital admission