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
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