The Direct Oral Anticoagulation Versus Vitamin K Antagonist After Cardiac Surgery Trial (DANCE)

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 atrial fibrillation requiring oral anticoagulation.

Study Overview

• Status: Recruiting
• Conditions: Bleeding Post Cardiac Surgery; Indication for Anticoagulation
• Intervention / Treatment: Drug: DOAC; Drug: VKA

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 that recruited 4811 patients from 105 centres in 27 countries, 77% of patients with AF on OAC were discharged on a VKA after cardiac surgery. Among patients taking a DOAC preoperatively, 55% were switched to a VKA after surgery. Over the first post-operative year, most of those patients were gradually transitioned back to a DOAC. Although effective, the use of VKAs 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.

A subset of 910 DANCE participants with a recent bioprosthetic aortic and/or mitral valve replacement will be enrolled in the SUNDANCE substudy (Subclinical valve thrombosis in patients with surgical bioprosthetic valve replacement: An imaging substudy of the DANCE trial). SUNDANCE will examine the effects of DOACs versus VKAs on subclinical valve thrombosis and bioprosthetic valve function by conducting computed tomography (CT) scans and echocardiograms at 60 to 90 days after randomization.

• Study Type: Interventional
• Enrollment (Estimated): 3500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Emilie Belley-Côté, MD, MSc; Phone Number: 40306 905-527-4322; Email: emilie.belley-cote@phri.ca
• Study Contact Backup: Name: Richard Whitlock, MD, PhD; Phone Number: 40306 905-527-4322; Email: richard.whitlock@phri.ca

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital Melbourne
      • Contact: Andrew Newcomb, MD
      • Principal Investigator: Andrew Newcomb, MD
    • Parkville, Victoria, Australia, 3050
      • Not yet recruiting
      • Royal Melbourne Hospital, University of Melbourne
      • Contact: Alistair Royse, MD
      • Principal Investigator: Alistair Royse, MD
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • Recruiting
      • University of Alberta Hospital
      • Principal Investigator: Steven Meyer, MD
      • Contact: Steven Meyer, MD
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • Recruiting
      • University of British Columbia
      • Principal Investigator: Erica Wang, PharmD
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Recruiting
      • St. Boniface Hospital
      • Principal Investigator: Michael Yamashita, MD
      • Contact: Michael Yamashita, MD
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L4L2
      • Active, not recruiting
      • Saint John Regional Hospital
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Recruiting
      • Health Science Centre
      • Principal Investigator: Hasib Hanif, MD
  • Ontario
    • Greater Sudbury, Ontario, Canada, P3E 5J1
      • Recruiting
      • Health Sciences North Research Institute
      • Principal Investigator: Bindu Bittira, MD
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton General Hospital
      • Contact: Emilie Belley-Côté, MD, MSc; Phone Number: 40306 905-527-4322; Email: emilie.belley-cote@phri.ca
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital
      • Contact: Vivek Rao, MD
      • Principal Investigator: Vivek Rao, MD
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Hospital
      • Contact: Stephen Fremes, MD
      • Principal Investigator: Stephen Fremes, MD
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Recruiting
      • Montreal Heart Institute
      • Contact: Philippe Demers, MD
      • Principal Investigator: Philippe Demers, MD
    • Montreal, Quebec, Canada, H4J1C5
      • Active, not recruiting
      • Hopital Sacre-Coeur de Montreal
    • Québec, Quebec, Canada, G1V 4G5
      • Recruiting
      • IUCPQ-Ulaval
      • Contact: Eric Dumont, MD
      • Principal Investigator: Eric Dumont, MD
• Germany
  • Bonn, Germany, 53127
    • Active, not recruiting
    • University Hospital Bonn Heart Center
  • Essen, Germany, 45147
    • Not yet recruiting
    • West-German Heart and Vascular Center, University of Duisburg-Essen
    • Contact: Matthias Thielmann, MD, PhD
    • Principal Investigator: Matthias Thielmann, MD, PhD
  • Hamburg, Germany, 20246
    • Recruiting
    • University Medical Center Hamburg-Eppendorf
    • Contact: Simon Pecha, MD
    • Principal Investigator: Simon Pecha, MD
  • Saxony
    • Leipzig, Saxony, Germany, 04289
      • Active, not recruiting
      • Heart Center Leipzig
  • Thuringia
    • Jena, Thuringia, Germany, Germany
      • Recruiting
      • University Hospital Jena
      • Contact: Torsten Doenst, MD, PhD
      • Principal Investigator: Torsten Doenst, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years at the time of enrolment,
2. Open heart surgery in the last 10 days,
3. Atrial fibrillation requiring anticoagulation (including pre-existing or post-operative atrial fibrillation),
4. Informed consent from either the patient or a substitute decision-maker.

Exclusion Criteria:

1. Mechanical valve replacement,
2. Antiphospholipid syndrome (triple positive),
3. Severe renal failure (Cockcroft-Gault equation; creatinine clearance <15 ml/min),
4. Known significant liver disease (Child-Pugh classification B and C),
5. Left ventricular thrombus,
6. Ongoing bleeding, hemorrhagic disorders, or bleeding diathesis,
7. Known contraindication for any DOAC or VKA,
8. Women who are pregnant, breastfeeding, or of childbearing potential,
9. Surgery including left ventricular assist device implantation or cardiac transplantation,
10. Previously enrolled in this trial,
11. Follow-up not possible,
12. History of moderate or severe mitral valvular lesion (stenosis or regurgitation) that is not corrected during index cardiac surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Apixaban; Dabigatran; Edoxaban; Rivaroxaban
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: Warfarin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Bleeding	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 (as defined by the International Society of Thrombosis and Hemostasis)	30-Days post-randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite of stroke and non-central nervous system systemic arterial embolism at 30 and 90 days.	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 arterial embolism	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	6 Months post-randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minor Bleeding	Tertiary outcome	30-Days and 90-Days post-randomization
All bleeding (major plus minor)	Tertiary outcome	30-Days and 90-Days post-randomization
Myocardial Infarction		30-Days and 90-Days post-randomization
Valve Thrombosis	Tertiary outcome	30-Days and 90-Days post-randomization
Hemorrhagic stroke	Tertiary outcome	30-Days and 90-Days post-randomization
All Stroke	Tertiary outcome	30-Days and 90-Days post-randomization
All Arterial Thrombosis/thromboembolism	Tertiary outcome: ischemic stroke, systemic arterial embolism, myocardial infarction, valve thrombosis	30-Days and 90-Days post-randomization
Quality of Life - EQ-5D-5L	Tertiary outcome: Measured by The EQ-5D-5L Questionnaire	30-Days and 90-Days post-randomization
Patient Satisfaction with Anticoagulant treatment	Tertiary outcome: Assessed by the Perception of Anticoagulant Treatment Questionnaire	30-Days and 90-Days post-randomization
Subclinical Valve Thrombosis on CT scan	Substudy outcome	60 to 90-Days post-randomization
Mean Aortic Valve g=Gradient on echocardiogram	Substudy outcome	60 to 90-Days post-randomization
Aortic Valve Reintervention	Substudy outcome	60 to 90-Days post-randomization
Association between subclinical valve thrombosis and clinically significant aortic valve thrombosis, stroke or systemic embolism		90 days

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Emilie Belley-Côté, MD, MSc, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: February 24, 2020
• First Posted (Actual): February 26, 2020

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Bleeding; Direct Oral Anticoagulant; Vitamin K Antagonist
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hemorrhage; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Morpholines; Oxazines; Thiophenes; Coumarins; Benzopyrans; 4-Hydroxycoumarins; Rivaroxaban; Dabigatran; Warfarin; apixaban; edoxaban
• Other Study ID Numbers: DANCE-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will establish a plan for the full-scale study but there is no plan to make IPD available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No