FDA lets CoreValve TAVI trial drop medical therapy randomization

[Lynlw]

http://www.theheart.org/article/1174205.do

In a move that will no doubt leave investigators sighing with relief, the FDA has granted permission for the US pivotal trial of Medtronic's CoreValve device to drop its planned randomization of patients to the device vs best medical therapy, allowing all of the "inoperable" patients in this arm of the trial to get the device [1].

That decision comes in the wake of the overwhelmingly positive results from the PARTNER cohort B trial using the rival Sapien transcatheter aortic-valve device (Edwards Lifesciences). That trial saw a 46% relative risk reduction in mortality (a 20% absolute difference) and a 61% relative risk reduction in cardiovascular mortality among patients randomized to the valve device instead of best medical therapy.

According to the announcement today, the CoreValve trial will still randomize high surgical-risk patients to either conventional aortic-valve surgery or percutaneous valve implantation, with 395 patients per group. (The parallel trial for the Sapien device, known as PARTNER cohort A, randomizing patients between device or surgery, is ongoing, and results are expected to be released at the ACC 2011 meeting/i2 Summit.)

But so-called "extreme-risk" patients in the CoreValve trial deemed too high risk for surgery by two surgeons at each site will instead be entered into a registry, where they will all receive a transcatheter aortic-valve implantation (TAVI) with the CoreValve device. In all, the device registry arm will enroll 487 subjects.

Speaking with heartwire, Dr Jeffrey Popma (Beth Israel Deaconess Medical Center, Boston, MA), national co-principal investigator for the CoreValve trial, which has yet to receive a catchy acronym, was clearly delighted by the announcement.

"AT TCT we learned from the PARTNER cohort B results in inoperable patients, which would be comparable to our 'extreme-risk' patients, that the mortality benefit for patients was dramatic, both in terms of the quality of life as well as the number of years that patients lived; that was a big deal," Popma said. "We learned there were 20 patients lives saved for every 100 patients treated, leaving a number needed to treat of five. At the end of the presentation, it was pretty clear that it would be difficult for us to [ask patients to consent to enroll] in any kind of a randomized clinical trial and suggest to those patients that there was any kind of clinical equipoise, that there was still some scientific question that needed to be addressed with respect to whether or not they were going to benefit from a percutaneous valve. Clearly they were. . . . I think many clinicians were very concerned about the mandatory randomization to medical therapy in a group that you knew had a 50% chance of dying within the next year."....

.....The trial is still in the process of "activating" the planned 40 US sites and starting enrollment of patients, Popma said. A company spokesperson confirmed to heartwire that the company hopes to complete enrollment in 2012; Popma anticipated being able to present results within one year of completing patient enrollment. Medtronic says it is aiming to have the device on the US market by 2014; it is already CE Mark approved in Europe.....

more at link

 

[normofthenorth]

Fascinating, and Good News, too. In surfing across www.theheart.org including that article, I found a number of other interesting "hits" including the following: www.theheart.org/article/1110833.do = "Cath labs should use both CoreValve and Sapien, small study concludes". Both give some insight to the "war" between CE & Medtronics (etc.) for future business from the likes of us!

That article also wonders "out loud" what the hospitals that only use one of the valves do, when they encounter a patient who isn't eligible for their valve, but could be helped by the competing valve. Good Question!! With conventional valves, it seems that many surgeons, groups, and hospitals, have strong allegiance to one supplier. With these new trans-cath valves, it seems that those allegiances will work strongly against the interest of patients -- as they may already be doing, with conventional heat valves! Too bad the contact between Big Pharma and "our" doctors is so extensive and so unregulated, I'd say! Or maybe improved communication -- like ours here -- can help solve the problem. . .

Here, people often advise newbies to get a second opinion, or to find a surgeon who's got experience with a different valve. I guess there aren't many patients who absolutely COULDN'T be helped with a CE valve, or with a Medtronics valve, or whatever, but I've never heard of a single case of one surgeon, or group, telling a patient to check out a different surgeon, or group, because they use a valve that might be a better "fit" for that patient. Anybody heard of ONE case of that?

 

[Jkm7]

Mass General and Brigham and Womens (among many other hospitals) are in the Partners Organization.

There is also a community hospital north of Boston Called North Shore Medical Center (in Salem and in Lynn, MA) that have been rated very high nationally. They, too, are part of Partners and are doing excellent OHS including valve replacements. I think they're the only Community Hospitals in MA to be so ranked and probably will be (or are already) involved in percutaneos valve placements.
What I wonder about is if surgeons have an incentive to drag their heels promoting percutaneous placement as who will be doing them? Cardiothoracic surgeons in OR's and/or Operating Rooms or Intensivist Cardiologists in the Cath Lab?

 

[Lynlw]

Mass General and Brigham and Womens (among many other hospitals) are in the Partners Organization.

There is also a community hospital north of Boston Called North Shore Medical Center (in Salem and in Lynn, MA) that have been rated very high nationally. They, too, are part of Partners and are doing excellent OHS including valve replacements. I think they're the only Community Hospitals in MA to be so ranked and probably will be (or are already) involved in percutaneos valve placements.
What I wonder about is if surgeons have an incentive to drag their heels promoting percutaneous placement as who will be doing them? Cardiothoracic surgeons in OR's and/or Operating Rooms or Intensivist Cardiologists in the Cath Lab?

you can see which hospitals are taking part in the trials at the clinic trial site here is the link for the Sapien partner trials http://www.clinicaltrials.gov/ct2/show/study/NCT00530894?term=sapien&rank=1&show_locs=Y#locn and the 26 centers are at the bottom of the page.
Here is the Corevalve trials that is just starting http://clinicaltrials.gov/ct2/show/study/NCT01240902?term=corevalve&rank=4&show_locs=Y#locn the 41 centers that WILL be part of the trials (most have not started recruiting yet) are at the bottom, I think as time goes on more centers will be involved like happened with the Partner trials

As for who and where..it depends on the centers, in the US at least many of the larger centers that are doing them have built brand new state of the art Hybrid suites that can be set up for caths or surgeries..(or start as a cath then move right to surgery with out moving the patient) IF it helps to picture how they do it CHOP has a cool link to see the hybrid suites http://www.chop.edu/flash/cardiac-virtual-tour.html this goes to the main page so just click on hybrid, cath or which ever room you want to check out

so far at least it is a team approach with inteventional cardiologist and surgeons working together. A few of the different conferences or panel discussion I've watched discussing this have talked about maybe starting a new training for surgeons to do more percutaneous procedures etc. They usually compare it to how things changed as more patients started to have their CABGs in the cath lab and not need OHS.