DOAC vs Warfarin as Blood Thinners After Heart Surgery

(DANCE Trial)

Recruiting at 20 trial locations

Overseen By Emilie Belley-Cote, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Population Health Research Institute

Must be taking: Anticoagulants

Disqualifiers: Mechanical valve, Renal failure, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

3500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two blood thinners after heart surgery for individuals with atrial fibrillation, a type of irregular heartbeat. It compares direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) to determine which is safer in the first 30 days post-surgery. Individuals who have undergone open heart surgery in the last 10 days and require blood thinners due to atrial fibrillation may be suitable candidates. The trial aims to identify the best option for preventing blood clots during recovery. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves comparing different blood thinners, you may need to switch to the study medication.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that direct oral anticoagulants (DOACs) are generally safe for heart-related issues. Studies comparing DOACs to older drugs like warfarin find that DOACs often cause fewer serious bleeding problems, addressing a common concern with blood thinners.

The FDA has already approved DOACs for other heart conditions, indicating their safety for people. Since their introduction in 2010, over ten years of data have provided insights into their effects and safety.

DOACs are often chosen for their ease of use and predictable performance. Unlike warfarin, they don't require frequent blood tests. For those considering a trial with DOACs, strong evidence supports their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DOACs (Direct Oral Anticoagulants) because they offer a fresh approach to blood thinning after heart surgery compared to the more traditional Vitamin K Antagonists (VKAs) like warfarin. Unlike VKAs, which require regular blood monitoring and dose adjustments to maintain the right INR range, DOACs are more straightforward, with fixed dosing and fewer dietary restrictions. This makes them much easier to manage for both doctors and patients. Plus, DOACs have a faster onset of action and a more predictable response, potentially leading to improved safety and convenience.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation after heart surgery?

This trial will compare the effectiveness of direct oral anticoagulants (DOACs) with warfarin as blood thinners after heart surgery. Studies have shown that DOACs reduce major brain-related events and bleeding problems more effectively than warfarin in patients with atrial fibrillation, a type of irregular heartbeat. Research indicates that DOACs are significantly more effective than warfarin in these areas. Specifically, one study found that using DOACs after surgery led to better results and fewer bleeding issues. Overall, DOACs offer a promising alternative to traditional blood thinners like warfarin, especially after heart surgery. ^{1 6 7 8 9}

Who Is on the Research Team?

Emilie Belley-Cote, MD, MSc

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had open heart surgery within the last 10 days and need blood thinners due to atrial fibrillation. It's not for those with severe kidney or liver disease, ongoing bleeding issues, mechanical heart valves, or women who are pregnant or could become pregnant.

Inclusion Criteria

I have not had open heart surgery in the last 10 days.

I have atrial fibrillation and need blood thinners.

Informed consent from either the patient or a substitute decision-maker

Exclusion Criteria

It's not possible to keep in touch with you after the study.

Previously enrolled in this trial

My kidneys are not working well (creatinine clearance <30 ml/min).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a direct oral anticoagulant (DOAC) or a vitamin K antagonist (VKA) for 30 days post-cardiac surgery

4 weeks

Regular monitoring visits for INR and safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for bleeding and thromboembolic events

60 to 90 days

CT scans and echocardiograms for SUNDANCE substudy participants

Extension

Long-term follow-up for additional safety and efficacy outcomes, including patient satisfaction and quality of life assessments

Up to 90 days

What Are the Treatments Tested in This Trial?

Interventions

• DOAC
• VKA

Trial Overview

The DANCE Trial compares new blood thinners (DOAC) with traditional ones (VKA) right after cardiac surgery in patients with atrial fibrillation. Participants will be randomly assigned to one of these treatments to test safety over a period of 30 days.

How Is the Trial Designed?

Group I: Direct Oral Anticoagulation (DOAC) Active Control 1 Intervention

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.

Group II: Vitamin K Antagonist Placebo Group 1 Intervention

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

DOAC is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as DOACs for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism

Approved in United States as DOACs for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism
• Stroke prevention

Approved in Canada as DOACs for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism

Approved in Japan as DOACs for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism

Approved in China as DOACs for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism

Approved in Switzerland as DOACs for:

• Atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Published Research Related to This Trial

In a study of 51 patients undergoing dental extractions while on anticoagulants, there was no significant difference in postoperative bleeding events between those taking direct oral anticoagulants (DOACs) and those on vitamin K antagonists (VKAs).

Most bleeding events were mild and manageable with local hemostatic measures, indicating that dental extractions can be safely performed in patients on DOACs without needing to interrupt their anticoagulant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of dental extraction in patients undergoing anticoagulant oral direct treatment: a pilot study. Mauprivez, C., Khonsari, RH., Razouk, O., et al.[2022]

In a study of 325 patients on direct oral anticoagulants (DOACs) and 199 patients on vitamin K antagonists (VKAs), the 30-day rate of major bleeding was significantly lower in the DOAC group (0.57%) compared to the VKA group (3.62%), indicating that DOACs may be safer in the postoperative setting.

There were no arterial thromboembolic events (ATEs) in the VKA cohort, while the ATE rate in the DOAC cohort was 0.57%, suggesting that while DOACs carry some risk of thromboembolic events, they are associated with fewer major bleeding complications compared to VKAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative interruption of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: A comparative analysis. Shaw, JR., Zhang, T., Le Gal, G., et al.[2023]

Direct oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban are widely used for anticoagulation due to their ease of use and lack of monitoring, making it crucial for physicians to manage them effectively during the perioperative period.

In managing DOACs, the decision to continue or discontinue the medication depends on the type of surgery; minor procedures may not require stopping the drug, while major surgeries may necessitate discontinuation hours before, based on the drug's pharmacokinetics and the patient's renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Management of Direct Oral Anticoagulants (DOACs): A Systemic Review. Sunkara, T., Ofori, E., Zarubin, V., et al.[2020]

In a study of 194 patients who underwent cardiac surgery, the use of direct oral anticoagulants (DOACs) like apixaban and rivaroxaban showed a similar safety profile to warfarin, with no significant difference in major bleeding events (4.1% for DOACs vs. 2.1% for warfarin).

The DOAC cohort did not experience any thrombotic events, while 2.1% of the warfarin cohort had thrombotic complications, suggesting that DOACs may be at least as effective as warfarin in preventing such events post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of apixaban and rivaroxaban compared to warfarin after cardiac surgery. Naik, KD., Whitson, BA., McLaughlin, EM., et al.[2023]

Direct-acting oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban offer predictable dosing and fewer drug interactions compared to traditional anticoagulants, making them easier to use for preventing and treating blood clots.

However, DOACs can accumulate in patients with kidney issues, lack routine monitoring tests for their effects, and currently have no specific antidotes for reversing their effects in cases of overdose or severe bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. Gómez-Outes, A., Suárez-Gea, ML., Lecumberri, R., et al.[2022]

Direct oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban are more effective and safer than traditional vitamin K antagonists, as shown in studies involving over 71,000 patients.

DOACs significantly reduce the risk of serious bleeding complications, particularly intracerebral bleeding, making them the preferred choice for patients with non-valvular atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stroke prevention with direct oral anticoagulants in patients with non-valvular atrial fibrillation]. Hohnloser, SH., Vámos, M., Diener, HC.[2015]

New oral anticoagulants (NOACs/DOACs) like Dabigatran, Apixaban, and Rivaroxaban are more effective and safer than traditional vitamin K antagonists, and they do not require constant monitoring, making them easier to use in clinical practice.

While NOACs/DOACs are generally safe, their dosages need to be adjusted based on kidney or liver function, and there is currently no antidote for reversing their effects (except for dabigatran), which is important to consider in cases of bleeding or urgent medical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New oral anticoagulants (NOAC) in nephrology]. Bellasi, A., Di Lullo, L., Melfa, G., et al.[2017]

Patients undergoing dental extractions while on uninterrupted Direct-acting oral anticoagulants (DOACs) showed a statistically significant lower risk of bleeding compared to those on Vitamin K antagonists (VKAs), with a risk ratio of 0.68 based on data from 539 DOAC patients and 574 VKA patients.

However, the overall quality of the evidence is very low, and the differences in bleeding risk among individual DOACs (like apixaban, rivaroxaban, dabigatran, and edoxaban) compared to VKAs were not statistically significant, indicating a need for further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bleeding Outcomes After Dental Extraction in Patients Under Direct-Acting Oral Anticoagulants vs. Vitamin K Antagonists: A Systematic Review and Meta-Analysis. Hua, W., Huang, Z., Huang, Z.[2021]

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