On-X Life Technologies Releases Expected Timelines for Reduced Anticoagulation Study

[Julian]

My futures so bright, I gotta wear shades. :cool2:

http://www.marketwatch.com/story/on-x-life-technologies-releases-expected-timelines-for-reduced-anticoagulation-study-results-at-aats-2012-04-30


press release

April 30, 2012, 7:59 a.m. EDT
On-X Life Technologies Releases Expected Timelines for Reduced Anticoagulation Study Results at AATS
Results for PROACT Trial Provide Sufficient Data to Permit Submission of Modified "Instructions for Use" to the FDA for the On-X Heart Valve for High-Risk Patients, as Well as Interim Results for Low-Risk (Aspirin and Clopidogrel) Patients

SAN FRANCISCO, Apr 30, 2012 (GlobeNewswire via COMTEX) -- On-X(R) Life Technologies, Inc. (On-X LTI) announced today that it is releasing the expected timelines for the initial submission to the FDA of modified "Instructions for Use" (IFU) of the On-X(R) Prosthetic Heart Valve based on data from the PROACT Anticoagulation Trial. The expected timelines are being provided to attendees of the 92nd Annual Meeting of the American Association for Thoracic Surgery (AATS) in the On-X Life Technologies exhibition booth number 517.

The first On-X Heart Valve IFU submission is based on the results of the High-Risk Aortic Valve Replacement Patient Group. It is anticipated that the submission will be made in the fall of 2012. The interim results report for the Low-Risk Aortic Valve Replacement Patient Group submission will follow in late 2012. The low-risk patients are being maintained with aspirin and clopidogrel only; no warfarin.

"The results of the PROACT trial appear thus far to be very positive," said Clyde Baker, On-X LTI's president. "The submission to the FDA of the IFU changes and the interim report for the aspirin and clopidogrel patient group will provide significant benefit to patients looking for a life-long correction of their valve problems, without the fear of reoperation in the next 10-15 years. Further, these clinical results are expected to have a very positive effect on the market penetration of the On-X valve and the growth of the company."

To obtain a copy of the expected timelines, contact On-X Life Technologies at [email protected] or (888) 339-8000.

More on the PROACT Trial

The preliminary report of PROACT (Prospective Randomized On-X Valve Anticoagulation Clinical Trial) data presented at the American College of Cardiology meeting in 2011 for the high-risk aortic patient test will provide the basis for modification of the IFU for the On-X Prosthetic Heart Valve. The modifications are expected to recommend that aortic valve replacement patients may be safely maintained at anticoagulation levels previously considered below professional society guidelines.

As had been hypothesized at the outset of the trial, patients in the test group with INRs between 1.5 and 2.0 are currently equal in composite thromboembolism and hemorrhage rates compared to the control group of patients. All patients received an On-X valve as a replacement for their aortic valve. High-risk aortic patients are those who have a higher potential for thrombotic or bleeding events. These were randomized into Test and Control groups for the trial. Both patient groups were maintained with standard anticoagulation therapy for the first three months after surgery and then randomized into their groups. The Test group was maintained with a daily dose of 81 milligrams of baby aspirin plus warfarin to achieve an INR target of 1.5 to 2.0. The Control group continued with standard anticoagulation therapy throughout the trial.

Present Guidelines (AHA/ACC) recommend patients with mechanical aortic valves be maintained at 2.0 to 2.5 INR. It is anticipated that with the lower levels of anticoagulation used during the PROACT trial that patients will experience fewer bleeding complications.

More about the On-X Prosthetic Heart Valve

The On-X valve is the result of a breakthrough in medical grade carbon technology--On-X(R) pure pyrolytic carbon. In addition to providing a more thromboresistant surface, the comparatively high strength of pure On-X(R) carbon enabled On-X LTI to make significant valve design changes that resulted in a prosthesis that acts more like a natural valve in its treatment of blood. It is well documented that the On-X valve does not produce the turbulence and blood damage commonly produced by other mechanical heart valve prostheses and, therefore, significantly reduces the potential for life-threatening blood clots.

About On-X LTI

On-X(R) Life Technologies, Inc. (On-X LTI) develops heart valve replacements that significantly improve the quality of life of patients. Jack Bokros, Ph.D., and his associates founded On-X LTI in 1994 to further advance prosthetic heart valve technology by capitalizing on their new form of pyrolytic carbon. The company has FDA, CE and Japanese approval for sale of the On-X(R) valve. On-X LTI also provides contract-manufacturing services utilizing its patented pyrolytic carbon to manufacturers of other medical products, including orthopedic joint and spine prostheses. Headquartered in Austin, Texas, On-X LTI is a privately held company. More information is located at www.onxlti.com .

The On-X Life Technologies Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=10418

On-X is a registered trademark of On-X Life Technologies, Inc. All other trademarks mentioned herein belong to their respective companies.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: On-X Life Technologies Inc.

 

[Bill B]

As had been hypothesized at the outset of the trial, patients in the test group with INRs between 1.5 and 2.0 are currently equal in composite thromboembolism and hemorrhage rates compared to the control group of patients. All patients received an On-X valve as a replacement for their aortic valve. High-risk aortic patients are those who have a higher potential for thrombotic or bleeding events.

I don't understand how this is a good thing or why a similar result wouldn't happen with any valve. If you reduce the intensity of anticoagulation, you would always expect throembolism rates to rise and hemmorhage rates to fall, so the composite would be the same. Why is this an advantage?

 

[TheGymGuy]

I don't understand how this is a good thing or why a similar result wouldn't happen with any valve. If you reduce the intensity of anticoagulation, you would always expect throembolism rates to rise and hemmorhage rates to fall, so the composite would be the same. Why is this an advantage?

Bill, it says that they are equal as compared to the ontrol group. What am I misreading?

 

[Julian]

Bill, it says that they are equal as compared to the ontrol group. What am I misreading?

Ya I didn't get it either, but then again I dropped out of college. What I got out of it was that the On-X has proved to perform just as well at lower INR levels vs standard recommend levels. That's a good thing, even though the other mechanical valves can probably do the same thing On-X has took a bold step to prove it and at this point will probably be the only valve to officially be approved for it in the very near future. In the end if this does and probably will happen On-X will take a share of the market and turn the heads of many surgeons that have been loyal to other brands.

 

[ElectLive]

On-X does a good job of never bothering to explain this, but Bill is exactly right, the composite is equal, not the rates individually, so overall performance is relative - it's both better and worse. See here for a pretty good discussion developing the point further: http://www.valvereplacement.org/forums/showthread.php?38184-On-X-clinical-study-interim-results&highlight=. You will find there the individual rates: higher thromboembolism (1.3% vs 0.4%) in the reduced INR group and higher hemorrhage (4.4% vs 2.5%) in the control group, as would logically be expected.

 

[Julian]

On-X does a good job of never bothering to explain this, but Bill is exactly right, the composite is equal, not the rates individually, so overall performance is relative - it's both better and worse. See here for a pretty good discussion developing the point further: http://www.valvereplacement.org/forums/showthread.php?38184-On-X-clinical-study-interim-results&highlight=. You will find there the individual rates: higher thromboembolism (1.3% vs 0.4%) in the reduced INR group and higher hemorrhage (4.4% vs 2.5%) in the control group, as would logically be expected.

Okay I think I get it now, so your saying that "Yay we have less bleeds!" but then "Boo we have more strokes!"??? In the end its a wash?

In the end we want to see strokes for strokes. We don't want to see composite numbers right?

People who had INR at 1.5 to 2.0 had just as many strokes as those 2.0 to 2.5. If we can see this then we can really tell if the valve is performing well right?

At this point the reports are saying people are having more strokes at lower INR levels vs recommended INR levels which is not a good thing and shows that the On-X valve has not shown an advantage. But because obviously lower INR levels are resulting in less bleeds lets combine the two numbers together and look like hero's right?

I've been duped, get this On-X flippin' valve out of my chest! KILL THE QUEEN!

 

[Julian]

TheGymGuy get your crap, you and I are going to the hospital right now and getting these On-X valves removed. We will not be made a fool of. We are more than just a pretty face. I know a place where we can get some good deals on St. Jude and ATS valves. You with me?

 

[chaconne]

The devil is in the details. We need to find out exactly what On-X is claiming to be better. If "composite" means bleeds + strokes, On-X's goal seems to be to reduce both by finding a window of operability where the combination of the two is at its lowest rate. If this is all true, this seems to be a good thing to me.

 

[Bill B]

I'm not saying there is ANYTHING wrong with the On-X valve compared to other valves. Let's not get carried away. It's just from the study results as On-X has described it, I see nothing to show it has any practical advantage. What I believe they are reporting, an increase in thromboembolism and a reduction in bleeding problems in the lower dose warfarin group, is something you would expect regardless of the particular valve and is not on its face a good thing. If over all morbidity, mortaility and medical costs were equal to the normal dose control group, then it just offers an alternative. If these things were found to be reduced (say, bleeding problems proved to be more traumatic and costly), then it would be an advantage. But I'm not sure they are looking at that. Yes, the devil is in the details, and I look forward to seeing them sometime in the future. In the meantime, I would never suggest anyone is making a mistake selecting this valve. I reviewed all of On-X's literature references and came to the conclusion that it's probably as good as any other of the major valves, but there is little evidence available showing superiority. http://billsworkshop.com/Some_AVR_lit/On-X refs.htm Valve replacement is a BIG business. Drug and device manufacturers OFTEN make claims that are not well substantiated to try to distinguish and promote their products over the alternatives. I worked in big pharma for 30 years and was involved in or saw a lot unbelievably clever and effective but weakly substantiated marketing programs, so I am more skeptical than a lot of other people. It is advisable to be very suspicious of manufacturer claims of superiority, even ones reviewed by the FDA (perhaps even more so, as the actual data are not published for direct review).

 

[chaconne]

I suppose it may come down to what you are more afraid of (bleed or stroke), as to whether the news is good or not. If you count them equally problematic, the On-X study may be showing positive results. I tend to be more afraid of stroke myself and don't want to increase my risk of that if I can help it.

 

[ElectLive]

Yes, the devil is in the details, and I look forward to seeing them sometime in the future.

Here is the On-X sanctioned interim overview with the individual rates I quoted: http://www.onxlti.com/2011/04/on-x-heart-valve-shows-safety-with-reduced-blood-thinners/.

Now, let's get to the good stuff, here are all the top secret details: http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_425310.pdf.

 

[Julian]

Here is the On-X sanctioned interim overview with the individual rates I quoted: http://www.onxlti.com/2011/04/on-x-heart-valve-shows-safety-with-reduced-blood-thinners/.

Now, let's get to the good stuff, here are all the top secret details: http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_425310.pdf.

I glanced over the top secret... What I gather overall is in order to see if On X is superior is by having the other valve companies do the same trial and see how they perform there is no other way to compare unless everyone wants to play baseball. I will give On-X a thumbs up for having the courage to even do this. This tells me they really believe. At this point we dont if St Jude, ATS, or Carbo would be able to perform at these levels. The lower you go the harder it is to keep the same results.

 

[Bill B]

Julian: I agree with your perspective. Nobody else has been willing to take the risk On-X is taking here. The other possible claim they could make despite the increased thromoembolic events in the low dose group versus control, is that the rate may still be less than has been seen with other valves. Making that kind of claim, which would have to be based on historical data, not a concurrent trial with the same patient population characteristics, is usually very debatable, but that is one way they might position this. I give On-X credit for trying this and for trying to advance mechanical valve design, even if ultimately it's not a true step forward in terms of measurable outcomes, as I have come to view it. On-X has an aggressive marketing program as exemplified by the paid patient survey announced at the top of each page here - a program only for new valve candidates (an obvious direct patient recruiting tool), and they have made claims for which I can find no proof. For example, they mention "soft closure" making the valve more quiet, but the only acoustic studies they cite don't show it to be more quiet. They claim superior hemodynamics, but the studies they cite don't generally support that - there are some other valves that do at least as well. Anyway, we each made our choice here. I don't feel at all bad about mine and neither should anyone choosing an On-X valve. GymGuy and I went around on this privately as he was making his choice. I gave him my perspective, which was not glowing but not negative either. He stayed with On-X. I don't think my valve is better. I chose it for other reasons.

 

[TheGymGuy]

TheGymGuy get your crap, you and I are going to the hospital right now and getting these On-X valves removed. We will not be made a fool of. We are more than just a pretty face. I know a place where we can get some good deals on St. Jude and ATS valves. You with me?

Ahahahahaa. I am with ya. STJ Regent is almost identical to On-X. I think one copied the other, though, I do not know who copied whom. My thinking is that if they are that similar I can wait a little longer for peer review of all this PROACT data.


EDITED TO ADD: Also, Bill B has documented and reviewed lots of literature at the link he provided above. I tend to believe that one mechanical valve is same as the other. It boils down to surgeon's choice and sometimes to personal preference. I seem to believe that newer which looks same as older is probably a better choice for me. Though, in the end, the biggest thing for me was going the mechanical route to avoid future re-ops.

 

[chaconne]

I think the On-X is certainly an interesting invention. Dr. Bokros, the inventor of the carbon that goes in all modern bi-leaflet mechanical valves, really seems to believe that his latest baby (the On-X), will prove to be better than the others. I had the opportunity to talk with him on the phone for about 30 minutes. He's a nice old guy and reminds me of the seasoned scientists and engineers I work with at JPL.

Even though the On-X seems to have features that make it superior, they may not make big enough difference among many other factors that can lead to clots such as the turbulence created when a bi-leaflet valve is opening or closing.

 

[Julian]

I think the On-X is certainly an interesting invention. Dr. Bokros, the inventor of the carbon that goes in all modern bi-leaflet mechanical valves, really seems to believe that his latest baby (the On-X), will prove to be better than the others. I had the opportunity to talk with him on the phone for about 30 minutes. He's a nice old guy and reminds me of the seasoned scientists and engineers I work with at JPL.

Even though the On-X seems to have features that make it superior, they may not make big enough difference among many other factors that can lead to clots such as the turbulence created when a bi-leaflet valve is opening or closing.

Chaconne, TheGymGuy and I are already on the way to the hospital to get our On-X valves removed. We can stop by and pick you up if you like. Let me know. :biggrin2:

 

[RobThatsMe]

I had a STJ aortic valve. It only lasted 10 yrs due to pannus growth around it.
I choose the ON-X when I replaced the STJ valve. The On-X design is supposed to help retard the growth of pannus.
My doctors say that if a person is prone to pannus, then the likely hood of it trying to come back remains.
So, since the STJ only lasted 10 yrs, I figured I had nothing to loose by trying the On-X design valve.

We shall see... and I will post my update on here in 8 more years.

Rob

 

[TheGymGuy]

Rob, I remember reading your story about that. I, personally, will be looking forward to your update in 8 years. I am sure things will be great. I really hope that the modification (lip) they added on ON-X really solves the pannus growth issues, they probably did a crap load of research and tests to come up with that.

 

[ElectLive]

Chaconne, TheGymGuy and I are already on the way to the hospital to get our On-X valves removed. We can stop by and pick you up if you like. Let me know. :biggrin2:

Just remember, you've been "duped" once already, so don't fall for any scratch and dent clearance deals on those St. Jude and ATS valves. Or even worse: giveaway used tissue valves... :biggrin2:

Great spirit and humor, Julian, as always, but you know, TheGymGuy is probably the only valver in history who might actually be physically and mentally up for this, so we should be careful not to put any ideas in his head...he might just want another shot at a Day 2 discharge.

 

[RobThatsMe]

Rob, I remember reading your story about that. I, personally, will be looking forward to your update in 8 years. I am sure things will be great. I really hope that the modification (lip) they added on ON-X really solves the pannus growth issues, they probably did a crap load of research and tests to come up with that.

Hi GymGuy,

Thanks. Hopefully there will not be any negative reports between now and then. So far, almost 2 years out, things are good.
I think those of us on the site with the On-X valves will be a great source of info for those considering one in the future.

Rob