At long last, CoreValve U.S. trial gets green light from FDA
Member rb305 mentioned his interest in this valve that's currently in use in Europe; the U.S. is now poised for its own trial.
October 15, 2010 | Reed Miller
Minneapolis, MN - The long-awaited US trial of the CoreValve transcatheter aortic-valve system is set to begin soon now that the FDA has granted Medtronic an investigational device exemption (IDE) for the pivotal study [1].
The study plan calls for two randomized cohorts. About 800 patients with severe aortic stenosis deemed "high risk" for aortic-valve surgery will be randomized in a 1:1 ratio to percutaneous implant of the CoreValve or surgical valve replacement. Another 400 patients at "extremely high risk" for aortic-valve surgery—"inoperable"—will be randomized in a 2:1 ratio to the CoreValve or medical management only, according to Medtronic
The co-primary end points for the inoperable cohort are all-cause death or major stroke at one year and a composite of all-cause death, major stroke, days of hospitalization for aortic-valve disease, and hospitalizations for aortic-valve disease at one year. For the high-risk cohort, the primary end point is all-cause mortality at one year.
The study, which the company expects to begin by the end of the fall, will be conducted at 40 US clinical sites and led by surgeon Dr David Adams (Mount Sinai Medical Center, New York) and interventionalist Dr Jeffrey Popma (Beth Israel Deaconess Medical Center, Boston, MA).
This two-cohort study is similar to the design of the PARTNER trial of the Edwards Sapien transcatheter aortic valve. Dramatic results in the inoperable patient arm of the study, released at the recent TCT 2010 conference, showed a 46% relative risk reduction in mortality (a 20% absolute difference) and a 61% relative risk reduction in cardiovascular mortality.
Since receiving CE Mark approval in 2007, the CoreValve system has been implanted in over 12 000 patients in 35 countries outside the US with encouraging results. Doctors in the US have been looking forward to the launch of the US trial for several years, as first CoreValve and then Medtronic, which bought CoreValve in 2009, worked to assure the FDA that the device was safe enough to enter a US pivotal clinical trial. For example, the FDA required the company to conduct preclinical bench testing of the device for 600 million cycles, which takes about six months, Dr John Liddicoat, vice president and general manager of Medtronic's structural heart division, told heartwire. He said that Medtronic "basically started over" with the IDE process when it bought CoreValve. At that time, Medtronic projected the FDA would approve this IDE in late summer 2010, so the process is almost right on schedule, he said.
Wells Fargo analyst Larry Biegelsen says Edwards will likely launch its Sapien valve in the US by the end of 2011, while Medtronic will probably earn FDA approval for the CoreValve no sooner than late 2014, which is consistent with Medtronic's projection.
Lessons learned
Popma told heartwire: "The FDA process has really led to a refinement of our clinical trial that will address the pertinent questions both in the extreme-risk—or inoperable—group as well as in the high-risk group and study the effectiveness of this device in these high-risk populations." The definitions of the end points for the study were developed with the FDA and the Valve Academic Research Consortium, an international group of experts in the field led by Dr Martin Leon (Columbia University, New York), Dr Mitchell Krucoff (Duke Clinical Research Institute, Durham, NC), Dr Donald Cutlip (Beth Israel Deaconess Hospital, Boston, MA), and Dr Patrick Serruys (Erasmus Medical Center, Rotterdam, the Netherlands). The company and CoreValve investigators say they've learned a lot from the experience with the device outside the US, leading, for example, to catheter design changes that help isolate the retractable delivery sheath from the introducer, allowing more precise placement of the device. The feedback from European users is that this "allows better placement with the device and more precise positioning."
Although only a few of the CoreValve investigators were involved with the PARTNER trial, the success of that study has informed the development of this CoreValve study, Popma said. "What we learned from PARTNER is that the prognosis associated with untreated aortic stenosis is very dismal," he said. "This is the right patient population to study, and we have the right device to study it, because relief of aortic stenosis physiologically has such a profound impact on mortality."
One important difference between the PARTNER study and the CoreValve study is that the latter trial will include major stroke as part of the composite secondary end point in the inoperable-patient cohort. "We want to appropriately incorporate the fact that a major stroke in an elderly patient is almost the same thing from the patient's perspective and quality of life as mortality," Popma said. "If we save more lives but have more strokes, then that's not really showing the benefit of the device."
Earlier this year, Medtronic announced the launch of SURTAVI, a large European, multicenter, randomized clinical trial comparing the CoreValve with surgical aortic replacement in a broad patient population, including moderate-risk patients. It will be led by Dr A Pieter Kappetein (Erasmus Medical Center, Rotterdam, the Netherlands), Dr Stephan Windecker (University Hospital, Bern, Switzerland), Dr Thomas Walther (University of Leipzig, Germany), and Dr Peter de Jaegere (Erasmus Medical Center).
Member rb305 mentioned his interest in this valve that's currently in use in Europe; the U.S. is now poised for its own trial.
October 15, 2010 | Reed Miller
Minneapolis, MN - The long-awaited US trial of the CoreValve transcatheter aortic-valve system is set to begin soon now that the FDA has granted Medtronic an investigational device exemption (IDE) for the pivotal study [1].
The study plan calls for two randomized cohorts. About 800 patients with severe aortic stenosis deemed "high risk" for aortic-valve surgery will be randomized in a 1:1 ratio to percutaneous implant of the CoreValve or surgical valve replacement. Another 400 patients at "extremely high risk" for aortic-valve surgery—"inoperable"—will be randomized in a 2:1 ratio to the CoreValve or medical management only, according to Medtronic
The co-primary end points for the inoperable cohort are all-cause death or major stroke at one year and a composite of all-cause death, major stroke, days of hospitalization for aortic-valve disease, and hospitalizations for aortic-valve disease at one year. For the high-risk cohort, the primary end point is all-cause mortality at one year.
The study, which the company expects to begin by the end of the fall, will be conducted at 40 US clinical sites and led by surgeon Dr David Adams (Mount Sinai Medical Center, New York) and interventionalist Dr Jeffrey Popma (Beth Israel Deaconess Medical Center, Boston, MA).
This two-cohort study is similar to the design of the PARTNER trial of the Edwards Sapien transcatheter aortic valve. Dramatic results in the inoperable patient arm of the study, released at the recent TCT 2010 conference, showed a 46% relative risk reduction in mortality (a 20% absolute difference) and a 61% relative risk reduction in cardiovascular mortality.
Since receiving CE Mark approval in 2007, the CoreValve system has been implanted in over 12 000 patients in 35 countries outside the US with encouraging results. Doctors in the US have been looking forward to the launch of the US trial for several years, as first CoreValve and then Medtronic, which bought CoreValve in 2009, worked to assure the FDA that the device was safe enough to enter a US pivotal clinical trial. For example, the FDA required the company to conduct preclinical bench testing of the device for 600 million cycles, which takes about six months, Dr John Liddicoat, vice president and general manager of Medtronic's structural heart division, told heartwire. He said that Medtronic "basically started over" with the IDE process when it bought CoreValve. At that time, Medtronic projected the FDA would approve this IDE in late summer 2010, so the process is almost right on schedule, he said.
Wells Fargo analyst Larry Biegelsen says Edwards will likely launch its Sapien valve in the US by the end of 2011, while Medtronic will probably earn FDA approval for the CoreValve no sooner than late 2014, which is consistent with Medtronic's projection.
Lessons learned
Popma told heartwire: "The FDA process has really led to a refinement of our clinical trial that will address the pertinent questions both in the extreme-risk—or inoperable—group as well as in the high-risk group and study the effectiveness of this device in these high-risk populations." The definitions of the end points for the study were developed with the FDA and the Valve Academic Research Consortium, an international group of experts in the field led by Dr Martin Leon (Columbia University, New York), Dr Mitchell Krucoff (Duke Clinical Research Institute, Durham, NC), Dr Donald Cutlip (Beth Israel Deaconess Hospital, Boston, MA), and Dr Patrick Serruys (Erasmus Medical Center, Rotterdam, the Netherlands). The company and CoreValve investigators say they've learned a lot from the experience with the device outside the US, leading, for example, to catheter design changes that help isolate the retractable delivery sheath from the introducer, allowing more precise placement of the device. The feedback from European users is that this "allows better placement with the device and more precise positioning."
Although only a few of the CoreValve investigators were involved with the PARTNER trial, the success of that study has informed the development of this CoreValve study, Popma said. "What we learned from PARTNER is that the prognosis associated with untreated aortic stenosis is very dismal," he said. "This is the right patient population to study, and we have the right device to study it, because relief of aortic stenosis physiologically has such a profound impact on mortality."
One important difference between the PARTNER study and the CoreValve study is that the latter trial will include major stroke as part of the composite secondary end point in the inoperable-patient cohort. "We want to appropriately incorporate the fact that a major stroke in an elderly patient is almost the same thing from the patient's perspective and quality of life as mortality," Popma said. "If we save more lives but have more strokes, then that's not really showing the benefit of the device."
Earlier this year, Medtronic announced the launch of SURTAVI, a large European, multicenter, randomized clinical trial comparing the CoreValve with surgical aortic replacement in a broad patient population, including moderate-risk patients. It will be led by Dr A Pieter Kappetein (Erasmus Medical Center, Rotterdam, the Netherlands), Dr Stephan Windecker (University Hospital, Bern, Switzerland), Dr Thomas Walther (University of Leipzig, Germany), and Dr Peter de Jaegere (Erasmus Medical Center).
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