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

Bleeding Post Cardiac Surgery Clinical Trial

— DANCE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04284839
• Other study ID #: DANCE-2020
• Status: Recruiting
• Phase: Phase 3
• Start date: July 18, 2021
• Est. completion date: June 2027

Study information

• Verified date: May 2024
• Source: Population Health Research Institute
• Contact: Emilie Belley-Cote, MD, MSc
• Phone: 905-527-4322
• Email: emilie.belley-cote[@]phri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 atrial fibrillation requiring oral anticoagulation.

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 valve replacement will be enrolled in the SUNDANCE substudy (Subclinical valve thrombosis in patients with surgical bioprosthetic aortic 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3500
• Est. completion date: June 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bleeding Post Cardiac Surgery
• Hemorrhage
• Indication for Anticoagulation

Intervention

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.
• VKA
Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range.

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	IUCPQ-ULaval	Quebec City	Quebec
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Boniface Hospital	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Population Health Research Institute	Hamilton Health Sciences Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minor Bleeding	Tertiary outcome	30-Days and 90-Days post-randomization
Other	All bleeding (major plus minor)	Tertiary outcome	30-Days and 90-Days post-randomization
Other	Myocardial Infarction		30-Days and 90-Days post-randomization
Other	Valve Thrombosis	Tertiary outcome	30-Days and 90-Days post-randomization
Other	Hemorrhagic stroke	Tertiary outcome	30-Days and 90-Days post-randomization
Other	All Stroke	Tertiary outcome	30-Days and 90-Days post-randomization
Other	All Arterial Thrombosis/thromboembolism	Tertiary outcome: ischemic stroke, systemic arterial embolism, myocardial infarction, valve thrombosis	30-Days and 90-Days post-randomization
Other	Quality of Life - EQ-5D-5L	Tertiary outcome: Measured by The EQ-5D-5L Questionnaire	30-Days and 90-Days post-randomization
Other	Patient Satisfaction with Anticoagulant treatment	Tertiary outcome: Assessed by the Perception of Anticoagulant Treatment Questionnaire	30-Days and 90-Days post-randomization
Other	Subclinical Valve Thrombosis on CT scan	Substudy outcome	60 to 90-Days post-randomization
Other	Mean Aortic Valve g=Gradient on echocardiogram	Substudy outcome	60 to 90-Days post-randomization
Other	Aortic Valve Reintervention	Substudy outcome	60 to 90-Days post-randomization
Other	Association between subclinical valve thrombosis and clinically significant aortic valve thrombosis, stroke or systemic embolism		90 days
Primary	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	Composite of stroke and non-central nervous system systemic arterial embolism at 30 and 90 days.		30-Days and 90-Days post-randomization
Secondary	Major Bleeding		90-Days post-randomization
Secondary	Pleural or pericardial effusion requiring drainage		30-Days and 90-Days post-randomization
Secondary	Systemic arterial embolism		30-Days and 90-Days post-randomization
Secondary	Ischemic stroke		30-Days and 90-Days post-randomization
Secondary	Deep vein thrombosis		30-Days and 90-Days post-randomization
Secondary	Pulmonary Embolism		30-Days and 90-Days post-randomization
Secondary	Length of post-operative hospital stay		30-Days and 90-Days post-randomization
Secondary	All-Cause Mortality		6 Months post-randomization