Atrial FibrillationPhase 2NCT05006287
The Safety of Non-vitamin K Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery
A Phase 2 study testing Non-vitamin K oral anticoagulants (NOACs) and Warfarin in people with Atrial Fibrillation, run by St. Paul's Hospital, Canada at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Non-vitamin K oral anticoagulants (NOACs) and Warfarin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 12 Oct 2022to 30 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years
- Cardiac surgical procedures
- Coronary artery bypass grafting (on or off pump)
- Bioprosthetic aortic valve replacement
- Mitral valve repair
- Ascending aorta procedures
Show all 13Show fewer
- Tricuspid valve repair
- Pulmonic valve procedures.
- An indication for oral anticoagulation
- Pre-existing AF
- New post-operative atrial fibrillation
- Arterial embolism
- Venous thromboembolism.
Who cannot join
- Cardiac surgical procedure
- Redo-sternotomy
- Bioprosthetic mitral valve replacement
- Mechanical valve replacement
- Transcatheter valve procedure
- Aortic arch procedures
Show all 20Show fewer
- 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
- Perioperative severe renal failure, defined as any eGFR <30 mL/min/1.73m2 or requirement of dialysis
- Perioperative liver failure with alanine aminotransferase > 3x upper limit of normal
- Pregnant or lactating women
- Patient unable to consent
- Contraindication to any study drug (including use of concomitant strong P-glycoprotein or cytochrome P450 enzyme inducers/inhibitors).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Trial of the Safety of Non-vitamin K Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery: a Pilot Study
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.
Read the detailed description
Patients undergoing cardiac surgery (CVS) have various indications for anticoagulation, with the most common being pre-existing atrial fibrillation (AF) or post-operative atrial fibrillation (POAF). The incidence of POAF is up to 42% and both pre-existing AF and POAF have been associated with 62% higher odds of stroke and 44% higher odds of mortality. Even though non-vitamin K oral anticoagulants (NOACs) have superseded warfarin as the choice anticoagulant for non-valvular AF based on the results of landmark trials, these trials generally excluded patients with recent CVS. Although recommendations on anticoagulation for POAF are extrapolated from general AF guidelines, there is hesitancy to use NOACs early after cardiac surgery due to concerns regarding hemorrhagic cardiac tamponade and the fast anticoagulant onset of these agents with limited access to reversal agents. The investigators recently conducted a systematic review of 7 studies evaluating NOACs in the post-CVS setting, which identified insufficient evidence regarding the safety and efficacy of NOACs versus warfarin. Despite there being 3 planned randomized controlled trials (RCT) comparing NOACs to warfarin early following cardiac surgery, none indicated a standardized bridging protocol, which is a significant limitation, as anticoagulation trials lacking in standardized bridging may significantly influence incidences of bleeding and embolic events. The investigators propose a multi-centered pilot RCT of 100 patients comparing NOACs to warfarin initiated early after cardiac surgery (ie. within the index hospitalization) to determine the feasibility of conducting a large, definitive RCT. Patients with an indication for anticoagulation (most common being pre-existing AF or POAF), will be randomized to receive a NOAC (starting on post-operative day [POD] 5 or later) or warfarin (starting on POD 1 or at time of diagnosis of indication for anticoagulation) and supported by a standardized bridging protocol with unfractionated heparin infusion or low molecular weight heparin as early as POD 3 in patients with high-risk of thrombosis and low risk of bleeding. The co-primary feasibility outcomes are (1) >70% of eligible patients recruited into the study, and (2) >80% adherence to the anticoagulation protocol (defined as adherence to the bridging protocol and the initiation of the study drug on the right POD). The primary scientific outcome is a composite of death, stroke or systemic embolism, major bleeding, or pericardial effusion requiring intervention. Follow up will be conducted at 1 and 3 months and corroborated by re-admission data. The results of this pilot RCT will inform the design and feasibility of a large definitive RCT.
- Conditions
- Atrial Fibrillation
- Being tested
- Non-vitamin K oral anticoagulants (NOACs), Warfarin
- Keywords
- postoperative anticoagulation, warfarin, NOAC, cardiac surgery, atrial fibrillation
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-vitamin K oral anticoagulants (NOACs)Drug
Also called Apixaban, Dabigatran, Edoxaban, Rivaroxaban
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.
WarfarinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Non-Vitamin K Oral Anticoagulant (NOAC) Group | Experimental | Anticoagulation with a NOAC (Apixaban, Dabigatran, Edoxaban, Rivaroxaban) Receives: Drug: Non-vitamin K oral anticoagulants (NOACs) |
| Warfarin Group | Active comparator | Anticoagulation with warfarin to target INR 2.5 Receives: Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful recruitment rate
The percentage of eligible participants who can be successfully recruited in the study
Measured: 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
Measured: 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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2021
- Study start12 Oct 2022
- Primary completion30 May 2024 (estimated)
- Study completion30 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- a multi-center, prospective, randomized, open-label, blinded-endpoint (PROBE) pilot study
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Paul's Hospital, Canada
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Ye, MD, St. Paul's Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05006287
- Sponsor's protocol ID
- StPaulH
- Status last verified
- Apr 2024
- First submitted
- 29 May 2021
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang EHZ, Turgeon R, Chu E, Sun T, Bashir J, Peng D, Cook R, Atherstone J, Gwozd T, Ye J. Direct Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery: A Pilot Randomized Controlled Trial. CJC Open. 2026 Mar 27;8(8):1109-1118. doi: 10.1016/j.cjco.2026.03.011. eCollection 2026 Aug.
PubMed 42610036
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of the Safety of Non-vitamin K Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery: a Pilot Study
- ClinicalTrials.gov ID
- NCT05006287
- Acronym / sponsor ID
- StPaulH
- Conditions
- Atrial Fibrillation
- Keywords
- postoperative anticoagulation, warfarin, NOAC, cardiac surgery, atrial fibrillation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (actual)
- Lead sponsor
- St. Paul's Hospital, CanadaUniversity, hospital or other
- Study start
- 12 Oct 2022 (actual)
- Primary completion
- 30 May 2024 (estimated)
- Study completion
- 30 May 2024 (estimated)
- First posted
- 16 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients undergoing cardiac surgery (CVS) have various indications for anticoagulation, with the most common being pre-existing atrial fibrillation (AF) or post-operative atrial fibrillation (POAF). The incidence of POAF is up to 42% and both pre-existing AF and POAF have been associated with 62% higher odds of stroke and 44% higher odds of mortality. Even though non-vitamin K oral anticoagulants (NOACs) have superseded warfarin as the choice anticoagulant for non-valvular AF based on the results of landmark trials, these trials generally excluded patients with recent CVS. Although recommendations on anticoagulation for POAF are extrapolated from general AF guidelines, there is hesitancy to use NOACs early after cardiac surgery due to concerns regarding hemorrhagic cardiac tamponade and the fast anticoagulant onset of these agents with limited access to reversal agents. The investigators recently conducted a systematic review of 7 studies evaluating NOACs in the post-CVS setting, which identified insufficient evidence regarding the safety and efficacy of NOACs versus warfarin. Despite there being 3 planned randomized controlled trials (RCT) comparing NOACs to warfarin early following cardiac surgery, none indicated a standardized bridging protocol, which is a significant limitation, as anticoagulation trials lacking in standardized bridging may significantly influence incidences of bleeding and embolic events. The investigators propose a multi-centered pilot RCT of 100 patients comparing NOACs to warfarin initiated early after cardiac surgery (ie. within the index hospitalization) to determine the feasibility of conducting a large, definitive RCT. Patients with an indication for anticoagulation (most common being pre-existing AF or POAF), will be randomized to receive a NOAC (starting on post-operative day [POD] 5 or later) or warfarin (starting on POD 1 or at time of diagnosis of indication for anticoagulation) and supported by a standardized bridging protocol with unfractionated heparin infusion or low molecular weight heparin as early as POD 3 in patients with high-risk of thrombosis and low risk of bleeding. The co-primary feasibility outcomes are (1) >70% of eligible patients recruited into the study, and (2) >80% adherence to the anticoagulation protocol (defined as adherence to the bridging protocol and the initiation of the study drug on the right POD). The primary scientific outcome is a composite of death, stroke or systemic embolism, major bleeding, or pericardial effusion requiring intervention. Follow up will be conducted at 1 and 3 months and corroborated by re-admission data. The results of this pilot RCT will inform the design and feasibility of a large definitive RCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- a multi-center, prospective, randomized, open-label, blinded-endpoint (PROBE) pilot study
| Arm | Type | Receives |
|---|---|---|
| Non-Vitamin K Oral Anticoagulant (NOAC) Group | Experimental | Drug: Non-vitamin K oral anticoagulants (NOACs)Anticoagulation with a NOAC (Apixaban, Dabigatran, Edoxaban, Rivaroxaban) |
| Warfarin Group | Active comparator | Drug: WarfarinAnticoagulation with warfarin to target INR 2.5 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adults ≥18 years
- Cardiac surgical procedures
- An indication for oral anticoagulation
Key exclusion criteria (20 listed)
- Cardiac surgical procedure
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-vitamin K oral anticoagulants (NOACs)Also: Apixaban, Dabigatran, Edoxaban, RivaroxabanNOAC 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. | Drug | Non-Vitamin K Oral Anticoagulant (NOAC) Group |
| WarfarinWarfarin 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. | Drug | Warfarin Group |
Primary outcome
Successful recruitment rate
Time frame: At study completion (ie. 3 months)
The percentage of eligible participants who can be successfully recruited in the study
Adherence rate to the anticoagulation protocol
Time frame: At study completion (ie. 3 months)
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
Composite safety endpoint
Time frame: 3 months
The percentage of participants who experience all-cause mortality, major bleeding, stroke or systemic embolism, pericardial effusion requiring intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Derived from this study: PubMed 42610036Wang EHZ, Turgeon R, Chu E, Sun T, Bashir J, Peng D, Cook R, Atherstone J, Gwozd T, Ye J. Direct Oral Anticoagulants Compared to Warfarin Early After Cardiac Surgery: A Pilot Randomized Controlled Trial. CJC Open. 2026 Mar 27;8(8):1109-1118. doi: 10.1016/j.cjco.2026.03.011. eCollection 2026 Aug.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Non-vitamin K oral anticoagulants (NOACs) and Warfarin in people with Atrial Fibrillation, run by St. Paul's Hospital, Canada at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Successful recruitment rate (time frame: At study completion (ie. 3 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05006287, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.