DANCE: The Direct Oral Anticoagulation Versus Warfarin After Cardiac Surgery Trial
Study Details
Study Description
Brief Summary
The DANCE Trial is a multi-centre, randomized controlled trial comparing the safety of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) in the early period (30 days) after cardiac surgery in patients with an indication for oral anticoagulation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
Approximately 36,000 Canadian adults undergo cardiac surgery annually. Of these patients, about 10% have a prior history of atrial fibrillation (AF). In the early post-operative period after cardiac surgery, 30-60% of patients develop AF and, by the time of discharge, 32% of patients who underwent cardiac surgery have an indication for oral anticoagulation (OAC). AF is associated with a significantly higher risk of stroke, even when transient, and OAC is the standard for thromboembolic prevention in these patients. In the post-operative period, the balance of benefits and risks of OAC may differ and the safest and most effective OAC in that patient population is uncertain.
Vitamin K antagonists (VKAs), such as warfarin or coumadin, are the most used anticoagulants after cardiac surgery. In the Left Atrial Appendage Occlusion Study (LAAOS) III, 77% of patients with AF on OAC were discharged on a VKA after cardiac surgery with 55% of the patients presenting on a direct oral anticoagulant (DOAC) being switched to a VKA! Although effective, their use is limited by a narrow therapeutic index requiring frequent international normalized ratio (INR) measurements to ensure appropriate levels of anticoagulation. This key limitation leads to non-compliance and discontinuation. In addition, in the first 3 months after cardiac surgery, time in the therapeutic range is low, even with close monitoring by experienced prescribers.
In the last decade, DOACs - inhibitors of factor Xa or thrombin- have become broadly used in patients with AF. Treatment with a DOAC in patients with AF has been demonstrated to yield a lower risk of stroke or systemic embolism and a similar risk of major bleeding when compared to VKAs during long-term follow-up. Moreover, DOACs are more convenient for both patients and clinicians. They have a rapid onset of effect, fixed dosage that obviates the need for regular monitoring, and few interactions with food and other medications. In the postoperative setting, DOACs may also lead to shorter length of stay and reduced costs.
The purpose of this study is to establish whether DOACs are as safe as VKAs in the first few weeks after heart surgery. The results of this study will impact the treatment of hundreds of thousands of patients in the world every year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Direct Oral Anticoagulation (DOAC) Patients in the intervention group will receive a DOAC at doses recommended for the indication, adjusted for their renal function is required. The choice of DOAC will be at the discretion of the treating physician. |
Drug: DOAC
Patients will receive a DOAC at doses recommended for the indication, adjusted for their renal function is required. The choice of DOAC will be at the discretion of the treating physician.
Other Names:
|
| Placebo Comparator: Vitamin K Antagonist Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range. |
Drug: VKA
Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Major Bleeding [30-Days post-randomization]
Major bleeding over follow-up defined as bleeding that results in death and/or symptomatic bleeding in a critical area or organ 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 (as defined by the International Society of Thrombosis and Hemostasis)
Secondary Outcome Measures
- Composite of stroke and non-central nervous system systemic embolism [30-Days and 90-Days post-randomization]
- Major Bleeding [90-Days post-randomization]
- Pleural or pericardial effusion requiring drainage [30-Days and 90-Days post-randomization]
- Systemic thromboembolism [30-Days and 90-Days post-randomization]
- Ischemic stroke [30-Days and 90-Days post-randomization]
- Deep vein thrombosis [30-Days and 90-Days post-randomization]
- Pulmonary Embolism [30-Days and 90-Days post-randomization]
- Length of post-operative hospital stay [30-Days and 90-Days post-randomization]
- All-Cause Mortality [30-Days, 90- Days and 6 Months post-randomization]
Other Outcome Measures
- Minor Bleeding [30-Days and 90-Days post-randomization]
Tertiary outcome
- All bleeding (major plus minor) [30-Days and 90-Days post-randomization]
Tertiary outcome
- Myocardial Infarction [30-Days and 90-Days post-randomization]
- Valve Thrombosis [30-Days and 90-Days post-randomization]
Tertiary outcome
- Hemorrhagic stroke [30-Days and 90-Days post-randomization]
Tertiary outcome
- All Stroke [30-Days and 90-Days post-randomization]
Tertiary outcome
- All Arterial Thrombosis/thromboembolism [30-Days and 90-Days post-randomization]
Tertiary outcome: ischemic stroke, systemic thromboembolism, myocardial infarction, valve thrombosis
- Quality of Life - EQ-5D-5L [30-Days and 90-Days post-randomization]
Tertiary outcome: Measured by The EQ-5D-5L Questionnaire
- Patient Satisfaction with Anticoagulant treatment [30-Days and 90-Days post-randomization]
Tertiary outcome: Assessed by the Perception of Anticoagulant Treatment Questionnaire
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥18 years at the time of enrolment,
-
Open heart surgery in the last 7 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:
-
Mechanical valve replacement,
-
Antiphospholipid syndrome (triple positive),
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Severe renal failure (Cockcroft-Gault equation; creatinine clearance <30 ml/min),
-
Known significant liver disease (Child-Pugh classification B and C),
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Left ventricular thrombus,
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Ongoing bleeding, hemorrhagic disorders, or bleeding diathesis,
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Known contraindication for any DOAC or VKA,
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Women who are pregnant, breastfeeding, or of childbearing potential,
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Previously enrolled in this trial,
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Follow-up not possible.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hamilton General Hospital | Hamilton | Ontario | Canada | L8L 2X2 |
Sponsors and Collaborators
- Population Health Research Institute
- Hamilton Health Sciences Corporation
Investigators
- Principal Investigator: Emilie Belley-Cote, MD, MSc, McMaster University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DANCE-2020