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| ID | Type | Description | Link |
|---|---|---|---|
| G050208 | Other Identifier | FDA |
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| Name | Class |
|---|---|
| Clinipace Worldwide | INDUSTRY |
| Acelis Connected Health | UNKNOWN |
| WCG IRB | OTHER |
| Avania |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AVR Low Risk without warfarin | Experimental | AVR Low Risk without warfarin |
|
| AVR low risk with standard warfarin | Active Comparator | AVR low risk with standard warfarin |
|
| AVR High risk with lower warfarin | Experimental | AVR High risk with lower warfarin |
|
| AVR High Risk with standard warfarin | Active Comparator | AVR High Risk with standard warfarin |
|
| MVR with lower warfarin | Experimental | MVR with lower warfarin |
|
| MVR with standard warfarin | Active Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| On-X valve using reduced anticoagulation | Device | Valve replacement with antiplatelet agents or lowered warfarin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Thromboembolism | Percentage of events per patient year | 8 years |
| Valve Thrombosis | Percentage of events per patient year | 8 years |
| Bleeding Events | Percentage of events per patient year | 8 years |
| Measure | Description | Time Frame |
|---|---|---|
| Valve-Related Mortality | Percentage of events per patient year | 8 years |
| Valve Hemodynamics | Echocardiograpic measures of valve hemodynamics at 5 years |
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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:
Concomitant cardiac surgery is allowed
Adult patients
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Puskas, MD | MOUNT SINAI HOSPITAL | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tucson Medical Center | Tucson | Arizona | 85718 | United States | ||
| Southern Arizona VA Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30286937 | Background | Puskas JD; PROACT Investigators. Reply: Low-Thrombogenicity Mechanical Heart Valves: Which Antithrombotic Strategy? J Am Coll Cardiol. 2018 Oct 9;72(15):1879-1880. doi: 10.1016/j.jacc.2018.07.063. No abstract available. | |
| 24512654 | Result | Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014 Apr;147(4):1202-1210; discussion 1210-1. doi: 10.1016/j.jtcvs.2014.01.004. Epub 2014 Jan 12. |
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| ID | Title | Description |
|---|---|---|
| FG000 | AVR Low Risk Without Warfarin | AVR Low Risk without warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| FG001 | AVR Low Risk With Standard Warfarin |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Mar 3, 2014 |
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Number of participants below refers to randomized in all 3 study arms
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MVR with standard warfarin
|
|
| On-X Valve with Standard warfarin Therapy | Device | Valve replacement with standard dosage warfarin |
|
|
| 5 years |
| Tucson |
| Arizona |
| 85723 |
| United States |
| Loma Linda University | Loma Linda | California | 92354 | United States |
| Hartford Hospital | Hartford | Connecticut | 06102 | United States |
| Christiana Health Care Services | Newark | Delaware | 19713 | United States |
| Medstar Heart & Vascular Institute | Washington D.C. | District of Columbia | 20010 | United States |
| Shands Hospital - University of Florida | Gainesville | Florida | 32610 | United States |
| Cardiac Surgical Associates | Kissimmee | Florida | 34741 | United States |
| South Florida Heart & Lung | Miami | Florida | 33133 | United States |
| Florida Hospital | Orlando | Florida | 32803 | United States |
| Emory University | Atlanta | Georgia | 30365 | United States |
| St. Francis Heart Center | Indianapolis | Indiana | 46237 | United States |
| Cotton-O'Neil Clinical Research Center | Topeka | Kansas | 66604 | United States |
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Maine Medical Center | Portland | Maine | 04102 | United States |
| Brigham & Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| St. Joseph Mercy Hospital | Ann Arbor | Michigan | 48197 | United States |
| Mid America Heart institute | Kansas City | Missouri | 64111 | United States |
| Barnes Jewish Hospital - Washington University | St Louis | Missouri | 63110 | United States |
| New Mexico Heart Institute | Albuquerque | New Mexico | 87102 | United States |
| St. Luke's Roosevelt | New York | New York | 10025 | United States |
| Montefiore Medical Center | New York | New York | 10461 | United States |
| WakeMed | Raleigh | North Carolina | 27610 | United States |
| Duke University Medical Center | Raleigh | North Carolina | 27710 | United States |
| Novant Health | Winston-Salem | North Carolina | 27104 | United States |
| University Hospital - Cleveland | Cleveland | Ohio | 44106 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Ohio State University Medical Center | Columbus | Ohio | 43210 | United States |
| University of Oklahoma/VA Oklahoma City | Oklahoma City | Oklahoma | 73104 | United States |
| Providence Heart & Vascular Institute | Portland | Oregon | 97220 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Baylor Research Institute | Dallas | Texas | 75226 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| Texas Heart Institute | Houston | Texas | 77225 | United States |
| Texas Cardiac Center | Lubbock | Texas | 79410 | United States |
| Baylor Scott & White - Plano | Plano | Texas | 78093 | United States |
| Mary Washington Hospital | Fredericksburg | Virginia | 22401 | United States |
| Sentara Norfolk General Hospital | Norfolk | Virginia | 23507 | United States |
| Swedish Medical Center | Seattle | Washington | 98122 | United States |
| MultiCare Health System | Tacoma | Washington | 98415 | United States |
| West Virginia University | Morgantown | West Virginia | 26506 | United States |
| St. Luke's Aurora Health Care | Milwaukee | Wisconsin | 53215 | United States |
| University of Alberta | Edmonton | Alberta | 76G 2B7 | Canada |
| University of British Columbia | Vancouver | British Columbia | V6Z 1Y6 | Canada |
| London Health Science Centre | London | Ontario | N6A 5A5 | Canada |
| Ottawa Heart Institute | Ottawa | Ontario | K1Y 4W7 | Canada |
| IUCPQ Chirurgie Cardiaque | Québec | Quebec | G1V 4G5 | Canada |
| 29504958 | Result | Yanagawa B, Levitsky S, Puskas JD; PROACT Investigators. Reduced anticoagulation is safe in high-risk patients with the On-X mechanical aortic valve. Curr Opin Cardiol. 2015 Mar;30(2):140-145. doi: 10.1097/HCO.0000000000000149. |
| 29903344 | Result | Puskas JD, Gerdisch M, Nichols D, Fermin L, Rhenman B, Kapoor D, Copeland J, Quinn R, Hughes GC, Azar H, McGrath M, Wait M, Kong B, Martin T, Douville EC, Meyer S, Ye J, Jamieson WRE, Landvater L, Hagberg R, Trotter T, Armitage J, Askew J, Accola K, Levy P, Duncan D, Yanagawa B, Ely J, Graeve A; PROACT Investigators. Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement. J Am Coll Cardiol. 2018 Jun 19;71(24):2717-2726. doi: 10.1016/j.jacc.2018.03.535. |
| 39617318 | Derived | Ruel M, Chu MWA, Graeve A, Gerdisch MW, Damiano RJ Jr, Smith RL 2nd, Keeling WB, Wait MA, Hagberg RC, Quinn RD, Sethi GK, Floridia R, Barreiro CJ, Pruitt AL, Accola KD, Dagenais F, Markowitz AH, Ye J, Sekela ME, Tsuda RY, Duncan DA, Swistel DG, Harville LE, DeRose JJ, Lehr EJ, Alexander JH, Puskas JD; PROACT Mitral Investigators. Midterm survival, clinical, and hemodynamic outcomes of a novel mechanical mitral valve prosthesis. J Thorac Cardiovasc Surg. 2025 Oct;170(4):1060-1068.e3. doi: 10.1016/j.jtcvs.2024.11.029. Epub 2024 Nov 29. |
| 36610532 | Derived | Chu MWA, Ruel M, Graeve A, Gerdisch MW, Damiano RJ Jr, Smith RL 2nd, Keeling WB, Wait MA, Hagberg RC, Quinn RD, Sethi GK, Floridia R, Barreiro CJ, Pruitt AL, Accola KD, Dagenais F, Markowitz AH, Ye J, Sekela ME, Tsuda RY, Duncan DA, Swistel DG, Harville LE 3rd, DeRose JJ, Lehr EJ, Alexander JH, Puskas JD; PROACT Mitral Investigators. Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial. Ann Thorac Surg. 2023 Apr;115(4):929-938. doi: 10.1016/j.athoracsur.2022.12.031. Epub 2023 Jan 4. |
| 35101419 | Derived | Chu MWA, Ruel M, Graeve A, Gerdisch MW, Damiano RJ Jr, Smith RL 2nd, Keeling WB, Wait MA, Hagberg RC, Quinn RD, Sethi GK, Floridia R, Barreiro CJ, Pruitt AL, Accola KD, Dagenais F, Markowitz AH, Ye J, Sekela ME, Tsuda RY, Duncan DA, Swistel DG, Harville LE 3rd, DeRose JJ, Lehr EJ, Puskas JD; PROACT Mitral Investigators. WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial. Ann Thorac Surg. 2022 Jan 28:S0003-4975(22)00138-2. doi: 10.1016/j.athoracsur.2022.01.015. Online ahead of print. |
AVR low risk with standard warfarin
On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin
| FG002 | 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 |
| FG003 | 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 |
| FG004 | MVR With Lower Warfarin | MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| FG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | AVR Low Risk Without Warfarin | AVR Low Risk without warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | MVR With Lower Warfarin | MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| BG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Thromboembolism | Percentage of events per patient year | Posted | Number | %/patient years | 8 years |
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| Primary | Valve Thrombosis | Percentage of events per patient year | Numbers in parentheses are Linearized Occurrence Rates (LOR) | Posted | Number | %/patient years | 8 years |
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| Primary | Bleeding Events | Percentage of events per patient year | Posted | Number | Linearized Occurrence Rates (LOR): %/pat | 8 years |
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| Secondary | Valve-Related Mortality | Percentage of events per patient year | Posted | Number | %/patient years | 8 years |
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| Secondary | Valve Hemodynamics | Echocardiograpic measures of valve hemodynamics at 5 years | Posted | Mean | Standard Deviation | mmHg | 5 years |
|
Events occurrence rate is presented for each arm at the end of its follow-up period. Time frame/Follow-up duration is different for each study arms (due to dependency on enrollment rate and timing of follow-up cessation at each arm): Aortic arm Low Risk: 8.6 years Aortic arm High Risk: 9.2 years Mitral arm: 14.7
Adverse events are reported as simple occurrence rates.
"Other" Adverse Events were not collected in this study; only risks/events that are known as associated with heart valve replacement were reported and adjudicated (presented above). Classification of events was based on the AATS/STS guidelines categories and definitions rather than on serious/non-serious. The number of "Other" AEs is reported here as "0" because none were collected in the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AVR Low Risk Without Warfarin | AVR Low Risk without warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin | 5 | 99 | 13 | 99 | 0 | 0 |
| EG001 | 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 | 4 | 102 | 13 | 102 | 0 | 0 |
| EG002 | 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 | 10 | 185 | 38 | 185 | 0 | 0 |
| EG003 | 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 | 9 | 190 | 43 | 190 | 0 | 0 |
| EG004 | MVR With Lower Warfarin | MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin | 17 | 201 | 94 | 201 | 0 | 0 |
| EG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin | 23 | 200 | 89 | 200 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Paravaluvular Leak | Cardiac disorders | AATS/STS Guidelines | Systematic Assessment | "Any evidence of leakage of blood around the prosthesis between the sewing ring and native annulus" (Protocol, Section C, page 21 |
|
| Endocarditis | Cardiac disorders | AATS/STS Guidelines | Systematic Assessment | Documented evidence of infection of the prosthesis [Protocol, Section C, page 20] |
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| Congestive Heart Failure | Cardiac disorders | AATS/STS Guidelines | Systematic Assessment | Whether considered valve-related or not |
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| Other - Cardiovascular and Pulmonary | Cardiac disorders | AATS/STS Guidelines | Systematic Assessment | Complication or any new diagnosis that is not related to the prosthesis, but is important to subsequent morbidity and mortality of the patient (Protocol, Section C, Page 22) |
|
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Study collected/reported events based on AATS/STS Guidelines (events of interest, with no serious/non-serious distinction).
Enrollment started 2006 for 3 arms:
AVR Low Risk - Enrollment & follow-up terminated 2014, indication not pursued AVR High Risk - Enrollment ended 2009, follow up completed 2014, low INR indication granted MVR - Enrollment ended 2020, follow up completed 2023, indication not pursued
Total SAEs is total of all categories presented minus mortality
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Project Manager (Yael Goode) | Artivion | 8454800137 | Yael.Goode@Artivion.com |
| Jan 31, 2024 |
| Prot_ICF_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 18, 2011 | Jan 31, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006349 | Heart Valve Diseases |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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|
|
| OG004 | MVR With Lower Warfarin | MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| OG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin |
|
|
| MVR With Lower Warfarin |
MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| OG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin |
|
|
MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| OG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin |
|
|
| MVR With Lower Warfarin |
MVR with lower warfarin On-X valve using reduced anticoagulation: Valve replacement with antiplatelet agents or lowered warfarin |
| OG005 | MVR With Standard Warfarin | MVR with standard warfarin On-X Valve with Standard warfarin Therapy: Valve replacement with standard dosage warfarin |
|
|