Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
6,215
Countries
1
Sites
5
Patients with atrial fibrillation requiring anticoagulation.
The objective in the vanguard phase of the DANCE trial is to assess the feasibility of conducting a large randomized controlled trial (RCT) evaluating the safety of DOAC versus VKA after cardiac surgery in patients with AF requiring oral anticoagulation. The objectives in the full trial are to evaluate the safety of DO…
Key facts
- Sponsor
- Hamilton Health Sciences Corporation, Hamilton Health Sciences Corporation
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 25 Oct 2024 → ongoing
- Decision date (initial)
- 2023-11-02
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- McMaster Surgical Associates · Hamilton Academic Health Sciences Organization · Canadian Cardiovascular Society in association w Canadian Arrhythmia Network & BMS-Pfizer Alliance
External identifiers
- EU CT number
- 2023-504504-28-00
- ClinicalTrials.gov
- NCT04284839
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
The objective in the vanguard phase of the DANCE trial is to assess the feasibility of conducting a large randomized controlled trial (RCT) evaluating the safety of DOAC versus VKA after cardiac surgery in patients with AF requiring oral anticoagulation.
The objectives in the full trial are to evaluate the safety of DOAC versus VKA after cardiac surgery in patients with AF requiring anticoagulation.
Conditions and MedDRA coding
Patients with atrial fibrillation requiring anticoagulation.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10003658 | Atrial fibrillation | 100000004849 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | The Direct Oral Anticoagulation versus Vitamin K Antagonist after Cardiac Surgery Trial The DANCE vanguard will be a 2-year, 400-patient, multicentre, randomized controlled vanguard trial evaluating whether the DANCE protocol is feasible to proceed to a full, international, multicentre RCT. It will also inform the optimal design of the DANCE trial. The DANCE trial will be a randomized, prospective, open-label, blinded end-point (PROBE), multicentre non-inferiority clinical trial. The intervention of interest is DOAC compared to VKA. The drugs will be obtained locally. For patients allocated to the DOAC arm, the choice of DOAC will be at the discretion of the ordering physician. For patients allocated to the VKA arm, INR monitoring and VKA dosing will be as per local practice. The sample size for the full trial is 6215.
This is an open-label trial: after randomization, treatment allocation will not be concealed to the patient, medical team, data collectors, or investigators. Since INR has to be closely monitored, an open-label design is necessary to ensure feasibility with regard to cost and workload. Because blinding is impractical and expensive, DANCE will be conducted using a PROBE design with clear and objective outcome definitions. A blinded panel of clinicians will adjudicate bleeding and thromboembolic outcomes.
|
Randomised Controlled | None | Intervention: DOAC: Patients in the intervention group will receive a DOAC at doses recommended for AF, adjusted for their renal function, weight, age as required. The choice of DOAC will be at the discretion of the treating physician. This approach is key for maximal generalizability of the study results. Treatment in the DOAC group will start no earlier than postoperative day 5 (if the patient is stable from a bleeding perspective) or discharge, whichever occurs first. DOACs are obtained locally. The patient will remain on allocated DOAC for 90 days post-randomization. The choice of OAC therapy after this period will be decided after discussion between the patient and their treating physician. Control: VKA: Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range. VKA dosage and INR monitoring frequency will be as per local practice in the participating centre. Antiplatelet therapy will be used at the discretion of the treating physician. Timing of VKA initiation is at the discretion of the treating physician. The patient will remain on allocated VKA for 90 days post-randomization. The choice of OAC therapy after this period will be decided after discussion between the patient and their treating physician. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Age ≥18 years at the time of enrolment
- Open heart surgery in the last 10 days
- Atrial fibrillation requiring anticoagulation (including pre-existing or post-operative atrial fibrillation)
- Informed consent from either the patient or a substitute decision-maker.
Exclusion criteria 12
- Mechanical valve replacement
- Antiphospholipid syndrome (triple positive)
- Severe renal failure (Cockcroft-Gault equation; creatinine clearance <15 ml/min)
- Known significant liver disease (Child-Pugh classification B and C)
- Left ventricular thrombus
- Ongoing bleeding, hemorrhagic disorders, or bleeding diathesis
- Known contraindication for any direct oral anticoagulant or vitamin K antagonist
- Women who are pregnant, breastfeeding, or of childbearing potential
- Surgery including left ventricular assist device implantation or cardiac transplantation
- Previously enrolled in this trial
- Follow-up not possible
- History of moderate or severe rheumatic valvular lesion (stenosis or regurgitation) that is not corrected during index cardiac surgery
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Major bleeding at 30 days, defined as bleeding that results in death and/or symptomatic bleeding in a critical area or organ, bleeding into a surgical site requiring reoperation, bleeding leading to hospitalization (including presentation to an acute care facility without overnight stay) and/or bleeding that causes a drop in the hemoglobin level of 20g/L or more, or that which requires the transfusion of ≥2 units of packed red blood cells or whole blood
Secondary endpoints 3
- Composite of stroke and non-central nervous system systemic arterial embolism at 30 and 90 days. This is intended to be confirmatory as high quality evidence has demonstrated DOACs to be superior to VKAs for thromboembolic protection.
- Major bleeding at 90 days; pleural effusion requiring drainage, pericardial effusion requiring drainage, systemic arterial embolism, ischemic stroke, deep vein thrombosis, pulmonary embolism, all-cause mortality, length of postoperative hospital stay at 30 and 90 days; all-cause mortality at 6 months.
- Minor bleeding, all bleeding, myocardial infarction, valve thrombosis, hemorrhagic stroke, all stroke, all arterial thrombosis/thromboembolism (ischemic stroke, systemic arterial embolism, myocardial infarction, valve thrombosis), quality of life measured by the EQ-5D-5L questionnaire, patient satisfaction with their anticoagulant treatment as assessed by the Perception of Anticoagulant Treatment Questionnaire (PACT-Q) and aggregate costs for both groups at 30 and 90 days.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 13
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09781MIG · Substance
- Active substance
- Phenprocoumon
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09781MIG · Substance
- Active substance
- Phenprocoumon
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB29263 · Substance
- Active substance
- Rivaroxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25425 · Substance
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25417 · Substance
- Active substance
- Dabigatran
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25425 · Substance
- Active substance
- Apixaban
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB32701 · Substance
- Active substance
- Edoxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25417 · Substance
- Active substance
- Dabigatran
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB32701 · Substance
- Active substance
- Edoxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB29263 · Substance
- Active substance
- Rivaroxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 90 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Hamilton Health Sciences Corporation
- Sponsor organisation
- Hamilton Health Sciences Corporation
- Address
- 100 King Street West
- City
- Hamilton
- Postcode
- L8P 1A2
- Country
- Canada
Scientific contact point
- Organisation
- Hamilton Health Sciences Corporation
- Contact name
- Dr. Emilie Belley-Cote
Public contact point
- Organisation
- Hamilton Health Sciences Corporation
- Contact name
- Dr. Emilie Belley-Cote
Hamilton Health Sciences Corporation
- Sponsor organisation
- Hamilton Health Sciences Corporation
- Address
- 100 King Street West
- City
- Hamilton
- Postcode
- L8P 1A2
- Country
- Canada
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 1,000 | 5 |
| Rest of world
Canada, Russian Federation
|
— | 5,215 | — |
Investigational sites
University Hospital Jena KöR
Herz und Thoraxchirurgie, Am Klinikum 1, Lobeda, Jena
Universitaetsklinikum Bonn AöR
Cardiac Surgery, Venusberg-Campus 1, Venusberg, Bonn
University Medical Center Hamburg-Eppendorf
Cardiovascular Surgery, Martinistrasse 52, Eppendorf, Hamburg
Universitaetsklinikum Essen AöR
Thoracic and Cardiovascular, Hufelandstrasse 55, Holsterhausen, Essen
Herzzentrum Leipzig GmbH
Cardiac Surgery, Struempellstrasse 40a, Probstheida, Leipzig
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2024-10-25 | 2024-11-27 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-01 | Germany | Acceptable with conditions 2023-10-25
|
2023-11-02 |
| 2 | SUBSTANTIAL MODIFICATION | SM-6 | 2023-11-21 | Germany | Acceptable 2023-12-20
|
2023-12-22 |