Thromboembolism, Thrombosis
Conditions
Keywords
chronic anticoagulation, vitamin K antagonist, mechanical heart valve, CYP2C9, warfarin, tecarfarin, chronic kidney disease
Brief summary
TACT is a real world randomized controlled trial of tecarfarin, a novel vitamin K antagonist, vs. warfarin. The quality of anticoagulation control will be compared for the two groups of subjects who require chronic oral anticoagulation for a broad panel of indications.
Detailed description
This will be a randomized, parallel-arm, open-label study comparing the safety and efficacy of tecarfarin and warfarin in approximately 1000 subjects who have an indication for chronic oral anticoagulation. The study will be fully enriched with subjects who are taking at least one CYP2C9-interacting medication and have either chronic kidney disease stage 3 or 4 and/or a genetic variant allele for CYP2C9. The study will be conducted at approximately 140 sites with experience in the management of anticoagulation subjects. Eligible subjects will be randomized to receive either tecarfarin or warfarin for a period ranging from 6 months to a maximum of approximately 24 months.
Interventions
DRUGWarfarin
Warfarin is an oral vitamin K antagonist anticoagulant.
DRUGtecarfarin
Tecarfarin is an oral vitamin K antagonist anticoagulant
Sponsors
Espero Biopharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
General Screening Inclusion Criteria 1. Is male or female and at least 18 years of age. 2. Is able and willing to sign an IRB-approved written informed consent. 3. Is able and willing to follow instructions, to comply with protocol requirements, and to attend required study visits. 4. Is taking a CYP2C9-interacting medication (inhibitor, substrate, or inducer; see list in Appendix A) at the time of randomization and is expected to receive this medication chronically for the duration of the trial. 5. Has either 1. Chronic kidney disease stage 3 or 4 (eGFR ≥ 15 to \<60 mL/min/1.73 m2 at Screening based on central laboratory) and/or 2. A CYP2C9 genotype variant allele 6. (Only for warfarin experienced patients) Patient is considered poorly controlled on warfarin therapy as judged by the investigator, e.g. has at least 2 INR values out of target range within previous 12 months Anticoagulation-Related Inclusion Criteria 7. Requires chronic anticoagulation therapy. 8. Is willing to receive chronic anticoagulation investigational therapy for the duration of the study or, for warfarin-naïve DVT subjects, treating physician prescribed at least a 6-month treatment period with an oral anticoagulation agent. 9. Has one or more of the following indications for chronic oral anticoagulation: 1. Atrial fibrillation/flutter (paroxysmal, persistent or permanent), not due to a reversible cause, documented by electrocardiography (ECG) 2. Aortic and/or mitral prosthetic HV 3. History of venous thromboembolic disease 4. History of myocardial infarction or cardiomyopathy 5. Any another indication for which warfarin is approved or recommended, with Sponsor approval 10. Conforms to the following restrictions regarding vitamin-K containing dietary supplements: 1. If taking at Baseline (Visit 2), is willing to continue with consistent doses throughout the study 2. If not taking at Baseline (Visit 2), is willing to abstain from such supplements throughout the study General
Exclusion criteria
1. Is pregnant, nursing, or a woman of childbearing potential who cannot assure that they will not become pregnant for the duration of the study. 2. Has been treated with an investigational drug within 30 days or 5 half-lives, whichever is longer, at time of screening. Safety-Related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of time in the therapeutic range (TTR) for tecarfarin vs. warfarin for each treatment group in the randomized population | From the date of randomization until study termination, up to 24 months (1st month not included) | Interpolated and observed TTR will be calculated for the two treatment groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage TTR for tecarfarin vs. warfarin in the sub-population of patients who are taking a CYP2C9-interacting medication and have a CYP2C9 genotype variant allele | From the date of randomization until study termination, up to 24 months (1st month not included) | Interpolated and observed TTR will be calculated for the two treatment groups |
| Percentage TTR for tecarfarin vs warfarin for the sub-population of patients who are taking a CYP2C9-interacting medication and have chronic kidney disease stage 3 or 4 (eGFR ≥ 15 to <60 mL/min/1.73 m2) | From the date of randomization until study termination, up to 24 months (1st month not included) | Interpolated and observed TTR will be calculated for the two treatment groups |
| Percentage of patients with INR > 4.0 for tecarfarin vs. warfarin | From the date of randomization until study termination, up to 24 months (1st month not included) | Percentage of observations of patients with INR \> 4.0 will be calculated for the two treatment groups |
| Percentage of patients with INR > 5.0 | From the date of randomization until study termination, up to 24 months (1st month not included) | Percentage of observations of patients with INR \> 5.0 will be calculated for the two treatment groups |
| Time to first embolic event for tecarfarin vs. warfarin | From the date of randomization until study termination, up to 24 months | Time from enrollment until any embolic event (CVA, pulmonary embolism, peripheral embolism) while enrolled will be calculated for the two groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| The primary safety endpoint of this study is the time to the first BARC category 3-5 bleeding event. | From the date of randomization until study termination, up to 24 months | BARC category 3-5 bleeding events will be compared for the two treatment groups |
| The secondary safety endpoint of this study is the time to the first BARC category 2-5 bleeding event | From the date of randomization until study termination, up to 24 months | BARC category 2-5 bleeding events will be compared for the two treatment groups |
Outcome results
None listed