Severe BleedingNCT03537521
Reversal Agent Use in Patients Treated With Direct Oral Anticoagulants or Vitamin K Antagonists (RADOA). Focus on New Antidots
An observational study of Severe Bleeding and Urgent Surgery, run by Cardioangiologisches Centrum Bethanien.
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 Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Severe Bleeding, Urgent Surgery
- What is being tested?
- Urgent surgery which can not be postponed to the next 24 hrs
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Apr 2020to Apr 2023
- How long will I take part?
- 30 Days
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
About this study
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
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
Read the 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:
- 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
- Document the clinical course and outcome of urgent surgical interventions within 24 hours after admission in patients under DOA or VKA treatment.
- Characterisation of therapeutic strategies in stopping acute life-threatening bleeding including following agents and methods:
- blood transfusion,
- platelet concentrates
- reversal agents [e.g. vitamin K, prothrombin complex concentrate (PCC), activated PCC (aPCC), activated factor VII (aVII), fibrinogen concentrate, fresh frozen plasma (FFP)]
- specific antidots, e.g. idarucizumab, Andexanet alpha
- haemodialysis
- desmopressin
- tranexamic acid
- no specific treatment in respect to the above mentioned treatments (e.g. stop of medication and waiting until anticoagulant effect of DOA is decreased).
- Conditions
- Severe Bleeding, Urgent Surgery
- Being tested
- Urgent surgery which can not be postponed to the next 24 hrs
- Keywords
- severe bleeding, dabigatran, rivaroxaban, apixaban, edoxaban, PCC, aPCC, rVIIa, hemodialysis, antidots, idarucizumab, urgent surgery, andexanet alpha
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Urgent surgery which can not be postponed to the next 24 hrsProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: Urgent surgery which can not be postponed to the next 24 hrs | |
| 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 Receives: Procedure: Urgent surgery which can not be postponed to the next 24 hrs |
What is being measured
The primary outcome is the main question the study is designed to answer.
In hospital mortality up to 30 days after admission
Death rate (number of deaths)
Measured: up to 30 days after hospital admission
Secondary outcomes (10)
Stop of bleeding defined according to the treating physicians
Decission according to the treating physicians
Measured: up to 30 days after hospital admission
Fatality rate caused by unstoppable bleeding
Death rate (number of deaths)
Measured: up to 30 days after hospital admission
Use versus no use of reversal agents - difference in outcome?
documentation of use of reversal agents in eCRF
Measured: up to 30 days after hospital admission
Definition of supportive measures being effective in stopping bleeding
documentation of supportive measures in eCRF
Measured: up to 30 days after hospital admission
Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding
time frame until stop of bleeding
Measured: up to 30 days after hospital admission
Causality assessment: Relation of SAE to anticoagulant medication
Decission according to the treating physicians
Measured: up to 30 days after hospital admission
Blood loss, number of transfusions necessary
documentation of supportive measures in eCRF
Measured: up to 30 days after hospital admission
Satisfaction of surgeon during and after surgery concerning bleeding
Decission according to the treating physicians
Measured: up to 30 days after hospital admission
Use versus no use of reversal agents - difference in blood loss and number of transfusions
documentation of supportive measures in eCRF
Measured: up to 30 days after hospital admission
Delay in performance of surgery due to anticoagulation
time Frame documented in eCRF
Measured: up to 30 days after hospital admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study startApr 2020 (estimated)
- Primary completionApr 2022 (estimated)
- Study completionApr 2023 (estimated)
Why it stopped: due to corona pandemic crisis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
- Target duration
- 30 Days
Sponsor and investigators
- Lead sponsor
- Cardioangiologisches Centrum Bethanien
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edelgard Lindhoff-Last, Prof., Principal investigator, CCB Studienzentrum GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537521
- Sponsor's protocol ID
- RADOA.DOT
- Status last verified
- Jul 2020
- First submitted
- 15 May 2018
- Last updated
- 17 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32605708
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03537521
- Acronym / sponsor ID
- RADOA.DOT
- Conditions
- Severe Bleeding, Urgent Surgery
- Keywords
- severe bleeding, dabigatran, rivaroxaban, apixaban, edoxaban, PCC, aPCC, rVIIa
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: due to corona pandemic crisis
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cardioangiologisches Centrum BethanienUniversity, hospital or other
- Study start
- Apr 2020 (estimated)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 25 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- 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
- Document the clinical course and outcome of urgent surgical interventions within 24 hours after admission in patients under DOA or VKA treatment.
- Characterisation of therapeutic strategies in stopping acute life-threatening bleeding including following agents and methods:
- blood transfusion,
- platelet concentrates
- reversal agents [e.g. vitamin K, prothrombin complex concentrate (PCC), activated PCC (aPCC), activated factor VII (aVII), fibrinogen concentrate, fresh frozen plasma (FFP)]
- specific antidots, e.g. idarucizumab, Andexanet alpha
- haemodialysis
- desmopressin
- tranexamic acid
- 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
- Observational model
- Other
- Time perspective
- Prospective
- Target follow-up
- 30 Days
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DOA | – | Procedure: Urgent surgery which can not be postponed to the next 24 hrsN= 130 patients treated with direct oral anticoagulants (DOAC) with acute bleeding N= 65 patients treated with direct oral anticoagulants (DOAC) with urgent surgical intervention |
| VKA | – | Procedure: Urgent surgery which can not be postponed to the next 24 hrsN= 130 patients treated with vitamin K antagonists (VKA) with acute bleeding N= 65 patients treated with vitamin K antagonists (VKA) with urgent surgical intervention |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Urgent surgery which can not be postponed to the next 24 hrsThe 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. | Procedure or surgery | DOA, VKA |
Primary outcome
In hospital mortality up to 30 days after admission
Time frame: up to 30 days after hospital admission
Death rate (number of deaths)
10 secondary outcomes
Stop of bleeding defined according to the treating physicians
Time frame: up to 30 days after hospital admission
Fatality rate caused by unstoppable bleeding
Time frame: up to 30 days after hospital admission
Use versus no use of reversal agents - difference in outcome?
Time frame: up to 30 days after hospital admission
Definition of supportive measures being effective in stopping bleeding
Time frame: up to 30 days after hospital admission
Effectiveness of dialysis vs. no dialysis in case of dabigatran accumulation associated with bleeding
Time frame: up to 30 days after hospital admission
Causality assessment: Relation of SAE to anticoagulant medication
Time frame: up to 30 days after hospital admission
Blood loss, number of transfusions necessary
Time frame: up to 30 days after hospital admission
Satisfaction of surgeon during and after surgery concerning bleeding
Time frame: up to 30 days after hospital admission
Use versus no use of reversal agents - difference in blood loss and number of transfusions
Time frame: up to 30 days after hospital admission
Delay in performance of surgery due to anticoagulation
Time frame: up to 30 days after hospital admission
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Background: PubMed 32605708Lindhoff-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edelgard Lindhoff-Last, Prof. principal investigator
CCB Studienzentrum GmbH
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Bleeding and Urgent Surgery, run by Cardioangiologisches Centrum Bethanien.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In hospital mortality up to 30 days after admission (time frame: up to 30 days after hospital admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03537521, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2020.