Heart Valve Disease
Conditions
Keywords
valve, prosthesis, antithrombotics, randomized
Brief summary
Various patient groups with the On-X Valve can be maintained safely on lower doses of blood thinner(Coumadin®) or on antiplatelet drugs (aspirin/Plavix®) only rather than the standard dose of Coumadin and aspirin presently recommended by ACC/AHA or ACCP professional societies.
Detailed description
This is a longitudinal, randomized (randomization to occur at the 3-month follow-up) study comparing the On-X valve on low dose anticoagulation (test group) to concomitant control groups of On-X valves receiving standard Coumadin/aspirin therapy, and also to FDA objective performance criteria (OPC) for heart valve replacement. It is a multicenter study consisting of up to 50 centers in the United States, Canada, and Italy enrolling and randomizing no more than 1200 patients (200 in each of 6 groups). There are three test arms of the study: low risk aortic valve replacement, high risk aortic valve replacement, and mitral valve replacement. Each arm has an equivalent control. Test therapies are: low risk aortic valve replacement - aspirin/Plavix, high risk aortic valve replacement - Coumadin at INR of 1.5 to 2.0 plus aspirin, and mitral valve replacement - Coumadin at an INR of 2.0 to 2.5 plus aspirin. Follow-up will run for up to 8 years in each patient. Each arm is independent and the low risk aortic and high risk aortic arms are completed. The low risk aortic arm was closed early resulting in a reduction of the estimated total enrollment with randomization to 1000. The high risk arm is completed with FDA review and this arm had 375 randomized enrollees. The mitral arm continues to enroll with a planned randomized enrollment of 400.
Interventions
DEVICEOn-X valve using reduced anticoagulation
Valve replacement with antiplatelet agents or lowered warfarin
DEVICEOn-X Valve with Standard warfarin Therapy
Valve replacement with standard dosage warfarin
Sponsors
Clinipace Worldwide
Acelis Connected Health
WCG IRB
Avania
On-X Life Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
Number of participants below refers to randomized in all 3 study arms
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients requiring isolated aortic valve replacement (AVR), or isolated mitral valve replacement (MVR). * AVR patients receiving low dose or antiplatelet only anticoagulation will be divided into groups at low risk and high risk for thromboembolism with all patients being in the low risk group except for patients with the following conditions which place a patient in the high risk group: * Chronic atrial fibrillation * Left ventricular ejection fraction \< 30 % * Enlarged left atrium \>50mm diameter * Spontaneous echo contrasts in the left atrium * Vascular pathology * Neurological events * Hypercoagulability * Left or right ventricular aneurysm * Lack of platelet response to aspirin or clopidogrel * Women receiving estrogen replacement therapy * Concomitant cardiac surgery is allowed * Adult patients
Exclusion criteria
* Right side valve replacement * Double (aortic plus mitral) valve replacement * Patients with active endocarditis at the time of implant * Previous confirmed or suspected thromboembolic event or thrombophlebitis * Other terminal illness * Patients who are in an emergency state * Inability to return for required follow-ups * Patients with an On-X valve implanted within the study and subsequently explanted * Patients who are known to be pregnant, plan to become pregnant or are lactating * Patients with acquired immunodeficiency syndrome or know to be HIV positive * Patients who are prison inmates or known drug or alcohol abusers * Patients unable to give adequate informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thromboembolism | 8 years | Percentage of events per patient year |
| Valve Thrombosis | 8 years | Percentage of events per patient year |
| Bleeding Events | 8 years | Percentage of events per patient year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Valve-Related Mortality | 8 years | Percentage of events per patient year |
| Valve Hemodynamics | 5 years | Echocardiograpic measures of valve hemodynamics at 5 years |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AVR Low Risk Without Warfarin AVR Low Risk without warfarin
On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin | 99 |
| AVR Low Risk With Standard Warfarin AVR low risk with standard warfarin
On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin | 102 |
| AVR High Risk With Lower Warfarin AVR High risk with lower warfarin
On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin | 185 |
| AVR High Risk With Standard Warfarin AVR High Risk with standard warfarin
On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin | 190 |
| MVR With Lower Warfarin MVR with lower warfarin
On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin | 201 |
| MVR With Standard Warfarin MVR with standard warfarin
On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin | 200 |
| Total | 977 |
Baseline characteristics
| Characteristic | Total | AVR Low Risk With Standard Warfarin | AVR High Risk With Lower Warfarin | AVR Low Risk Without Warfarin | AVR High Risk With Standard Warfarin | MVR With Lower Warfarin | MVR With Standard Warfarin |
|---|---|---|---|---|---|---|---|
| Age, Customized | 54.3 years STANDARD_DEVIATION 11.7 | 52.5 years STANDARD_DEVIATION 11.6 | 54.1 years STANDARD_DEVIATION 13 | 53.5 years STANDARD_DEVIATION 10.9 | 55.8 years STANDARD_DEVIATION 12 | 55.0 years STANDARD_DEVIATION 11.2 | 54.9 years STANDARD_DEVIATION 11.6 |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — | — | — | — |
| Sex: Female, Male Female | 367 Participants | 26 Participants | 37 Participants | 23 Participants | 36 Participants | 121 Participants | 124 Participants |
| Sex: Female, Male Male | 610 Participants | 76 Participants | 148 Participants | 76 Participants | 154 Participants | 80 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 99 | 4 / 102 | 10 / 185 | 9 / 190 | 17 / 201 | 23 / 200 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 13 / 99 | 13 / 102 | 38 / 185 | 43 / 190 | 94 / 201 | 89 / 200 |
Outcome results
Primary
Bleeding Events
Percentage of events per patient year
Time frame: 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVR Low Risk Without Warfarin | Bleeding Events | 3.82 Linearized Occurrence Rates (LOR): %/pat |
| AVR Low Risk With Standard Warfarin | Bleeding Events | 3.49 Linearized Occurrence Rates (LOR): %/pat |
| AVR High Risk With Lower Warfarin | Bleeding Events | 2.86 Linearized Occurrence Rates (LOR): %/pat |
| AVR High Risk With Standard Warfarin | Bleeding Events | 7.43 Linearized Occurrence Rates (LOR): %/pat |
| MVR With Lower Warfarin | Bleeding Events | 9.63 Linearized Occurrence Rates (LOR): %/pat |
| MVR With Standard Warfarin | Bleeding Events | 10.01 Linearized Occurrence Rates (LOR): %/pat |
Primary
Thromboembolism
Percentage of events per patient year
Time frame: 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVR Low Risk Without Warfarin | Thromboembolism | 4.86 %/patient years |
| AVR Low Risk With Standard Warfarin | Thromboembolism | 0.29 %/patient years |
| AVR High Risk With Lower Warfarin | Thromboembolism | 2.43 %/patient years |
| AVR High Risk With Standard Warfarin | Thromboembolism | 1.74 %/patient years |
| MVR With Lower Warfarin | Thromboembolism | 2.48 %/patient years |
| MVR With Standard Warfarin | Thromboembolism | 2.08 %/patient years |
Primary
Valve Thrombosis
Percentage of events per patient year
Time frame: 8 years
Population: Numbers in parentheses are Linearized Occurrence Rates (LOR)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVR Low Risk Without Warfarin | Valve Thrombosis | 0.69 %/patient years |
| AVR Low Risk With Standard Warfarin | Valve Thrombosis | 0.87 %/patient years |
| AVR High Risk With Lower Warfarin | Valve Thrombosis | 0.21 %/patient years |
| AVR High Risk With Standard Warfarin | Valve Thrombosis | 0.37 %/patient years |
| MVR With Lower Warfarin | Valve Thrombosis | 0.46 %/patient years |
| MVR With Standard Warfarin | Valve Thrombosis | 0.40 %/patient years |
Secondary
Valve Hemodynamics
Echocardiograpic measures of valve hemodynamics at 5 years
Time frame: 5 years
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVR Low Risk Without Warfarin | Valve Hemodynamics | Peak Gradient mmHg | 22.64 mmHg | Standard Deviation 11.74 |
| AVR Low Risk Without Warfarin | Valve Hemodynamics | Mean Gradient mmHg | 11.38 mmHg | Standard Deviation 6.25 |
| AVR Low Risk With Standard Warfarin | Valve Hemodynamics | Mean Gradient mmHg | 11.00 mmHg | Standard Deviation 5.87 |
| AVR Low Risk With Standard Warfarin | Valve Hemodynamics | Peak Gradient mmHg | 21.31 mmHg | Standard Deviation 12.24 |
| AVR High Risk With Lower Warfarin | Valve Hemodynamics | Peak Gradient mmHg | 15.8 mmHg | Standard Deviation 9.8 |
| AVR High Risk With Lower Warfarin | Valve Hemodynamics | Mean Gradient mmHg | 7.6 mmHg | Standard Deviation 5 |
| AVR High Risk With Standard Warfarin | Valve Hemodynamics | Peak Gradient mmHg | 16.7 mmHg | Standard Deviation 8.5 |
| AVR High Risk With Standard Warfarin | Valve Hemodynamics | Mean Gradient mmHg | 8.8 mmHg | Standard Deviation 4.2 |
| MVR With Lower Warfarin | Valve Hemodynamics | Peak Gradient mmHg | 11.9 mmHg | Standard Deviation 4.4 |
| MVR With Lower Warfarin | Valve Hemodynamics | Mean Gradient mmHg | 4.6 mmHg | Standard Deviation 1.93 |
| MVR With Standard Warfarin | Valve Hemodynamics | Mean Gradient mmHg | 4.7 mmHg | Standard Deviation 1.98 |
| MVR With Standard Warfarin | Valve Hemodynamics | Peak Gradient mmHg | 12.6 mmHg | Standard Deviation 7.5 |
Secondary
Valve-Related Mortality
Percentage of events per patient year
Time frame: 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVR Low Risk Without Warfarin | Valve-Related Mortality | 0.69 %/patient years |
| AVR Low Risk With Standard Warfarin | Valve-Related Mortality | 0.87 %/patient years |
| AVR High Risk With Lower Warfarin | Valve-Related Mortality | 0.21 %/patient years |
| AVR High Risk With Standard Warfarin | Valve-Related Mortality | 0.37 %/patient years |
| MVR With Lower Warfarin | Valve-Related Mortality | 0.28 %/patient years |
| MVR With Standard Warfarin | Valve-Related Mortality | 0.10 %/patient years |