Randy & Robyn
Well-known member
As promised, here are the results for the 1st year of the On-X aspirin study.
I look forward to seeing your opinions. My thinking is that, for a select group of recipients with no other medical complications, the outlook is hopeful. But with the limited number of patient years it must still be considered inconclusive.
Update: On-X Aortic Valve Aspirin Study ?
One Year Anniversary
Prepared by Medical Carbon Research Institute, L.L.C.
Distributed November 15, 2004
Announcement
Medical Carbon Research Institute L.L.C. (MCRITM), manufacturer of the On-X® Prosthetic Heart Valve this month recognized the one-year anniversary of the initiation of an aspirin-only anticoagulation study in Germany. The initiation of the On-X valve aspirin study with the approval of the German Ethics Commission based in Freiburg and by the individual participating German hospitals? local Ethics Committees is the first such study to be approved by a regulatory agency for any mechanical heart valve. The fact that complications within a valve trial occur in greatest frequency within the first six months to one year makes this anniversary very significant. To date, patients within the study, with only one exception, have experienced no serious adverse events, suggesting that the study objective is achievable.
Study Objective
The objective of the study is to determine if the material and design of the On-X mechanical heart valve has evolved sufficiently to allow for an aspirin-only anticoagulation regimen making it possible for selected simple aortic valve replacement patients to use 100 mg/d of aspirin rather than warfarin-based anticoagulation, which is currently the standard of care for all mechanical valves. This study was designed to test the On-X aortic mechanical valve under an anticoagulation protocol normally used with biological valves.
Current Results of this Study
The study currently has a total patient experience of 15 pt/yrs, the first patient being placed on the aspirin protocol 13 months ago. Trends from the study will start to be apparent at 100 pt/yrs of experience, which should be achieved within the next 12 to 18 months.
Except for one adverse event (described below), all other patients have been on aspirin-only for a mean follow-up of 7.5 ± 2.9 (range: 6 to 13) months. Of the patients enrolled under the updated exclusion criteria survival is 100 percent, transthoracic echo (TTE) shows normally functioning On-X valves in all patients, and mean LDH is 234 ± 22 (normal: <240) U/l. Of all patients enrolled since initiation of the aspirin study, survival is 95.2%. One aspirin-only patient with carotid atherosclerosis had a minor transient ischemic attack (TIA) lasting only a few minutes at six weeks follow-up. Other than this patient and the one described below, there have been no additional thromboembolic events, valve thromboses or other complications.
Adverse Event
The only serious adverse patient event occurred in April of 2004 wherein a patient died. By protocol, the study was placed in a state of ?suspension,? meaning that no additional patients could be entered into the study. Patients already converted to the aspirin-only protocol were informed of the event, given additional instruction in compliance to the protocol and required to sign an additional informed consent agreement in order to remain in the study.
After reviewing the facts relating to the event, the Data and Safety Monitoring Committee (DSMC) of the On-X Aortic Valve Aspirin Study recommended continuation of the study subject to the same ethics committee reviews and re-approvals. Having fully investigated the adverse event, the immediately involved hospital ethics committee has determined that the study may be resumed. The study was modified to exclude patients with potentially complicating conditions similar to those in the patient who died, including the exclusion of patients with permanent pacemakers and those with a combination of other conditions that may predispose them to coagulation related complications. In addition, more frequent monitoring of the patients was instituted.
Clinical Rationale for the Study
The Aspirin Study approval was based upon cumulative clinical experience with performance of the On-X valve in standard use, in animal models for thrombotic behavior and higher risk, non-compliant patient populations. This cumulative experience provided the basis for the belief that a reasonable potential existed that certain patients implanted with the On-X valve might be maintained without the use of warfarin. Details of some key research findings follow.
The South African Study
The South African study includes 526 patients, 300 of which received On-X valves between 1999 and 2004, with a maximum follow-up of 4.2 years. The On-X group is comprised of patients with varying amounts of anticoagulation. Because of poor compliance with anticoagulation protocols approximately 49 percent of On-X patients reported on thus far were categorized as having ?unsatisfactory? (less than 1.5 INR) anticoagulation. In spite of this, none of the patients receiving On-X valves have experienced thrombosis or bleeding. One aortic valve patient had a thromboembolic event, causing an overall rate of 1.3%/pt./yr.
Primary European FDA Trial
Data for isolated aortic and mitral valves from Medical Carbon Research Institute Application to the United States Food and Drug Administration for Pre-Market Approval (P000037), September 1, 2000, updated through July 1, 2001, further updated through May 31, 2003 (3.6 year mean follow-up; late [>30days] complications) are displayed in the table below:
On-X Valve Morbid Events
All Events (Major & Minor) >30 Days, %Per Pt-Yr
1,081 Pt-Yrs, Avg. Follow-up 3.6 Years
Event Aortic Mitral A+M
Thromboembolism 1.0 1.0 1.0
Thrombosis 0.0 0.0 0.0
Hemorrhage 0.6 0.5 0.6
Totals 1.6 1.5 1.6
Animal Model Test
A study of the valve in a sheep model designed to force valve thrombosis and to predict a valve?s resistance to thrombosis found that the On-X valve statistically outperformed other mechanical valves (From a Cox-Mantel test on the Kaplan-Meier curve p+0.0051). The first thrombosis of an On-X valve occurred at six weeks compared to two weeks for the other valves. Additionally, two of six On-X test valves survived the test without thrombosis compared to zero of seven for the other seven valves.
Aspirin Study Design
This is a longitudinal study comparing the On-X valve on aspirin (test group) to a concomitant, non-randomized control group of On-X valve recipients receiving standard Coumadin/warfarin therapy. Where feasible, it will be compared to FDA objective performance criteria and historical data on the On-X valve. The DSMC carefully considered the concept of randomization for the study and concluded that it was impractical to randomize because of the limited patient population that would meet inclusion/exclusion criteria.
A. Patient Inclusion
1. Isolated aortic valve replacement
2. Sinus rhythm
3. Concomitant bypass, septal defect repair, tricuspid or mitral repair allowed
4. Adult patients
B. Patient Exclusion
1. Multiple valve replacement
2. Chronic atrial fibrillation, ejection fraction <30%
3. Enlarged left atrium >50mm diameter
4. Spontaneous echo contrasts in the left atrium
5. Previous thromboembolic event
6. Vascular pathology or neurological events
7. Hypercoagulability
8. Ventricular aneurysm
9. Lack of therapeutic response to aspirin
10. Active endocarditis
11. Other terminal illness
12. Patients who are in an emergency state
13. Inability to return for required follow-ups
14. No prisoners, no persons unable to give adequate informed consent
15. Permanent cardiac pacemaker
All patients meeting the criteria were invited to participate as a test group patient. Those electing not to be in the test group were requested to participate in the control group with the identical follow-up schedule as the test group.
Follow-up Regime and Intervals
The intent of the study design is to treat mechanical valve patients in a manner identical to the treatment received by tissue valve patients. Therefore, the drug regime is generally consistent with the recommendations of the American College of Chest Physicians (ACCP) and the American College of Cardiology (ACC) for tissue valves. Patients were maintained on 100 mg of aspirin beginning immediately postoperatively. For the first three months postoperatively, patients were also given Coumadin/warfarin with an INR target of 2.5. INR was measured every two weeks up to the three-month follow-up at an anticoagulation clinic or like facility. Prior to weaning each patient from Coumadin/warfarin a platelet aggregation test was performed. If platelet function was normal despite the presence of aspirin, the patient was not to be included in the test group.
MCRI Contact
For additional information contact:
Clyde Baker
President
MCRI-On-X Valve
8200 Cameron Road, Suite A-196
Austin, Texas 78754-3823
Email: [email protected]
Phone: 512-339-8000 ext. 269
Fax: 512-339-3636
Mobile: 512-657-2214
www.onxvalves.com
www.mcritx.com
I look forward to seeing your opinions. My thinking is that, for a select group of recipients with no other medical complications, the outlook is hopeful. But with the limited number of patient years it must still be considered inconclusive.
Update: On-X Aortic Valve Aspirin Study ?
One Year Anniversary
Prepared by Medical Carbon Research Institute, L.L.C.
Distributed November 15, 2004
Announcement
Medical Carbon Research Institute L.L.C. (MCRITM), manufacturer of the On-X® Prosthetic Heart Valve this month recognized the one-year anniversary of the initiation of an aspirin-only anticoagulation study in Germany. The initiation of the On-X valve aspirin study with the approval of the German Ethics Commission based in Freiburg and by the individual participating German hospitals? local Ethics Committees is the first such study to be approved by a regulatory agency for any mechanical heart valve. The fact that complications within a valve trial occur in greatest frequency within the first six months to one year makes this anniversary very significant. To date, patients within the study, with only one exception, have experienced no serious adverse events, suggesting that the study objective is achievable.
Study Objective
The objective of the study is to determine if the material and design of the On-X mechanical heart valve has evolved sufficiently to allow for an aspirin-only anticoagulation regimen making it possible for selected simple aortic valve replacement patients to use 100 mg/d of aspirin rather than warfarin-based anticoagulation, which is currently the standard of care for all mechanical valves. This study was designed to test the On-X aortic mechanical valve under an anticoagulation protocol normally used with biological valves.
Current Results of this Study
The study currently has a total patient experience of 15 pt/yrs, the first patient being placed on the aspirin protocol 13 months ago. Trends from the study will start to be apparent at 100 pt/yrs of experience, which should be achieved within the next 12 to 18 months.
Except for one adverse event (described below), all other patients have been on aspirin-only for a mean follow-up of 7.5 ± 2.9 (range: 6 to 13) months. Of the patients enrolled under the updated exclusion criteria survival is 100 percent, transthoracic echo (TTE) shows normally functioning On-X valves in all patients, and mean LDH is 234 ± 22 (normal: <240) U/l. Of all patients enrolled since initiation of the aspirin study, survival is 95.2%. One aspirin-only patient with carotid atherosclerosis had a minor transient ischemic attack (TIA) lasting only a few minutes at six weeks follow-up. Other than this patient and the one described below, there have been no additional thromboembolic events, valve thromboses or other complications.
Adverse Event
The only serious adverse patient event occurred in April of 2004 wherein a patient died. By protocol, the study was placed in a state of ?suspension,? meaning that no additional patients could be entered into the study. Patients already converted to the aspirin-only protocol were informed of the event, given additional instruction in compliance to the protocol and required to sign an additional informed consent agreement in order to remain in the study.
After reviewing the facts relating to the event, the Data and Safety Monitoring Committee (DSMC) of the On-X Aortic Valve Aspirin Study recommended continuation of the study subject to the same ethics committee reviews and re-approvals. Having fully investigated the adverse event, the immediately involved hospital ethics committee has determined that the study may be resumed. The study was modified to exclude patients with potentially complicating conditions similar to those in the patient who died, including the exclusion of patients with permanent pacemakers and those with a combination of other conditions that may predispose them to coagulation related complications. In addition, more frequent monitoring of the patients was instituted.
Clinical Rationale for the Study
The Aspirin Study approval was based upon cumulative clinical experience with performance of the On-X valve in standard use, in animal models for thrombotic behavior and higher risk, non-compliant patient populations. This cumulative experience provided the basis for the belief that a reasonable potential existed that certain patients implanted with the On-X valve might be maintained without the use of warfarin. Details of some key research findings follow.
The South African Study
The South African study includes 526 patients, 300 of which received On-X valves between 1999 and 2004, with a maximum follow-up of 4.2 years. The On-X group is comprised of patients with varying amounts of anticoagulation. Because of poor compliance with anticoagulation protocols approximately 49 percent of On-X patients reported on thus far were categorized as having ?unsatisfactory? (less than 1.5 INR) anticoagulation. In spite of this, none of the patients receiving On-X valves have experienced thrombosis or bleeding. One aortic valve patient had a thromboembolic event, causing an overall rate of 1.3%/pt./yr.
Primary European FDA Trial
Data for isolated aortic and mitral valves from Medical Carbon Research Institute Application to the United States Food and Drug Administration for Pre-Market Approval (P000037), September 1, 2000, updated through July 1, 2001, further updated through May 31, 2003 (3.6 year mean follow-up; late [>30days] complications) are displayed in the table below:
On-X Valve Morbid Events
All Events (Major & Minor) >30 Days, %Per Pt-Yr
1,081 Pt-Yrs, Avg. Follow-up 3.6 Years
Event Aortic Mitral A+M
Thromboembolism 1.0 1.0 1.0
Thrombosis 0.0 0.0 0.0
Hemorrhage 0.6 0.5 0.6
Totals 1.6 1.5 1.6
Animal Model Test
A study of the valve in a sheep model designed to force valve thrombosis and to predict a valve?s resistance to thrombosis found that the On-X valve statistically outperformed other mechanical valves (From a Cox-Mantel test on the Kaplan-Meier curve p+0.0051). The first thrombosis of an On-X valve occurred at six weeks compared to two weeks for the other valves. Additionally, two of six On-X test valves survived the test without thrombosis compared to zero of seven for the other seven valves.
Aspirin Study Design
This is a longitudinal study comparing the On-X valve on aspirin (test group) to a concomitant, non-randomized control group of On-X valve recipients receiving standard Coumadin/warfarin therapy. Where feasible, it will be compared to FDA objective performance criteria and historical data on the On-X valve. The DSMC carefully considered the concept of randomization for the study and concluded that it was impractical to randomize because of the limited patient population that would meet inclusion/exclusion criteria.
A. Patient Inclusion
1. Isolated aortic valve replacement
2. Sinus rhythm
3. Concomitant bypass, septal defect repair, tricuspid or mitral repair allowed
4. Adult patients
B. Patient Exclusion
1. Multiple valve replacement
2. Chronic atrial fibrillation, ejection fraction <30%
3. Enlarged left atrium >50mm diameter
4. Spontaneous echo contrasts in the left atrium
5. Previous thromboembolic event
6. Vascular pathology or neurological events
7. Hypercoagulability
8. Ventricular aneurysm
9. Lack of therapeutic response to aspirin
10. Active endocarditis
11. Other terminal illness
12. Patients who are in an emergency state
13. Inability to return for required follow-ups
14. No prisoners, no persons unable to give adequate informed consent
15. Permanent cardiac pacemaker
All patients meeting the criteria were invited to participate as a test group patient. Those electing not to be in the test group were requested to participate in the control group with the identical follow-up schedule as the test group.
Follow-up Regime and Intervals
The intent of the study design is to treat mechanical valve patients in a manner identical to the treatment received by tissue valve patients. Therefore, the drug regime is generally consistent with the recommendations of the American College of Chest Physicians (ACCP) and the American College of Cardiology (ACC) for tissue valves. Patients were maintained on 100 mg of aspirin beginning immediately postoperatively. For the first three months postoperatively, patients were also given Coumadin/warfarin with an INR target of 2.5. INR was measured every two weeks up to the three-month follow-up at an anticoagulation clinic or like facility. Prior to weaning each patient from Coumadin/warfarin a platelet aggregation test was performed. If platelet function was normal despite the presence of aspirin, the patient was not to be included in the test group.
MCRI Contact
For additional information contact:
Clyde Baker
President
MCRI-On-X Valve
8200 Cameron Road, Suite A-196
Austin, Texas 78754-3823
Email: [email protected]
Phone: 512-339-8000 ext. 269
Fax: 512-339-3636
Mobile: 512-657-2214
www.onxvalves.com
www.mcritx.com
