The Safety of Non-vitamin K Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery

NCT05006287 | Active Not Recruiting Phase 2

• 1 other identifier: StPaulH
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

A small pilot study comparing different blood thinners (non-vitamin K oral anticoagulants \[NOACs\] and warfarin) will be conducted in people at risk for blood clots after open-heart surgery. This study will help us design a much bigger study to test the effectiveness and safety of different blood thinners in people after open-heart surgery. The study will test the following hypotheses: (1) Our standardized use of different blood thinners is feasible in patients early after cardiac surgery. (2) NOACs are safe to use early after cardiac surgery.

Conditions

Atrial Fibrillation

Keywords

postoperative anticoagulation; warfarin; NOAC; cardiac surgery; atrial fibrillation

Outcome Measures

Primary Outcomes (3)

• Successful recruitment rate

  The percentage of eligible participants who can be successfully recruited in the study

  At study completion (ie. 3 months)

• Adherence rate to the anticoagulation protocol

  The percentage of participants who are adherent to the pre-specified anticoagulation protocol (ie. day of initiation of NOAC or warfarin, indication and dosing of bridging) during index hospital stay

  At study completion (ie. 3 months)

• Composite safety endpoint

  The percentage of participants who experience all-cause mortality, major bleeding, stroke or systemic embolism, pericardial effusion requiring intervention

  3 months

Study Arms (2)

Non-Vitamin K Oral Anticoagulant (NOAC) Group

EXPERIMENTAL

Anticoagulation with a NOAC (Apixaban, Dabigatran, Edoxaban, Rivaroxaban)

Drug: Non-vitamin K oral anticoagulants (NOACs)

Warfarin Group

ACTIVE COMPARATOR

Anticoagulation with warfarin to target INR 2.5

Drug: Warfarin

Interventions

Non-vitamin K oral anticoagulants (NOACs) DRUG

NOAC Group (Intervention): Patients randomized to the NOAC group will receive a NOAC dosed according to the Canadian monograph for the respective indication. Patients receiving a NOAC before cardiac surgery will resume the same NOAC as pre-operatively, whereas patients not previously receiving a NOAC will preferentially receive apixaban according to local practice. The NOAC will be started no earlier than post-operative day 5 and based on the standard protocol depending on whether the patient has a pre-existing indication for anticoagulation or new indication (e.g. post-operative atrial fibrillation). Patients at high risk of thrombosis and low risk of bleeding will receive a standardized bridging protocol as early as post-operative day 3 with unfractionated heparin infusion or low molecular weight heparin until the NOAC is initiated.

Also known as: Apixaban, Dabigatran, Edoxaban, Rivaroxaban

Non-Vitamin K Oral Anticoagulant (NOAC) Group

Warfarin DRUG

Warfarin Group (Comparator): Patients randomized to the warfarin group will receive warfarin titrated to achieve a target International Normalized Ratio (INR) of 2.5 (range 2.0 to 3.0). Warfarin will be started as early as post-operative day 1 and based on the standard protocol depending on whether the patient has a pre-existing indication for anticoagulation or new indication (e.g. post-operative atrial fibrillation). Patients at high risk of thrombosis and low risk of bleeding will receive a standardized bridging protocol as early as post-operative day 3 with unfractionated heparin infusion or low molecular weight heparin until INR is 2.0 or above.

Warfarin Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years
• Cardiac surgical procedures
• Coronary artery bypass grafting (on or off pump)
• Bioprosthetic aortic valve replacement
• Mitral valve repair
• Ascending aorta procedures
• Tricuspid valve repair
• Pulmonic valve procedures.
• An indication for oral anticoagulation
• Pre-existing AF
• New post-operative atrial fibrillation
• Arterial embolism
• Venous thromboembolism.

You may not qualify if:

• Cardiac surgical procedure
• Redo-sternotomy
• Bioprosthetic mitral valve replacement
• Mechanical valve replacement
• Transcatheter valve procedure
• Aortic arch procedures
• Pericardectomy
• Post-operative extracorporeal membrane oxygenation
• Heart transplant
• Ventricular assist devices
• Congenital heart procedures
• Stroke within 4 weeks prior to surgery or postoperatively prior to initiation of study drug
• Recent history of heparin-induced thrombocytopenia (less than 3 months)
• High risk for bleeding (e.g. major bleed \[intracranial hemorrhage, gastrointestinal bleed\] within past 3 months, unexplained drop in hemoglobin pre-operatively)
• Postoperative bleeding requiring return to operating room for exploration prior to randomization

Sponsors & Collaborators

• St. Paul's Hospital, Canada: lead

Study Sites (1)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

apixaban; Dabigatran; edoxaban; Rivaroxaban; Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiac Surgery, Clinical Professor

Model Details: a multi-center, prospective, randomized, open-label, blinded-endpoint (PROBE) pilot study

Study Record Dates

• First Submitted: May 29, 2021
• First Posted: August 16, 2021
• Study Start: October 12, 2022
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)