In conjunction with yesterday's statements concerning renewed focus on the valve sector, Edwards Lifesciences (Irvine, California) also reported conditional FDA approval to begin a pivotal clinical trial of its Sapien transcatheter aortic heart valve technology.

For patients suffering from aortic stenosis — a narrowing of the valve that restricts blood flow — open-heart surgery may very well be the best option. But not all patients are good candidates for conventional valve replacement surgery. Edwards hopes the Sapien may be their answer.

The Placement of Aortic Transcatheter valves (PARTNER) trial will evaluate the Sapien in patients who are considered high risk for conventional open-heart surgery.

"We see this as bringing a very transformational technology to patients who either are not operable or elect not to undergo surgery. It's an opportunity to bring those untreatable patients into the treatment pool," Larry Wood, VP and general manager of Transcatheter Replacement at Edwards, told Medical Device Daily.

PARTNER is a randomized clinical trial essentially offering two studies. A surgical category of the study will enroll 350 high-risk patients who are candidates for conventional open-heart surgery. These patients will be evenly randomized to receive either the Edwards Sapien transcatheter heart valve or surgical valve replacement. The clinical results of this arm will need to demonstrate that the Sapien valve is not statistically inferior to conventional surgery.

The medical management study of the trial will enroll 250 patients who are considered too high risk for conventional open-heart surgery. Those patients will be evenly randomized to receive either the Edwards Sapien transcatheter heart valve or appropriate medical therapy, as prescribed by the physician. The clinical results of this arm will need to demonstrate that the Sapien valve is statistically superior to medical management.

The primary endpoint in both arms of the trial is mortality at one year with secondary endpoints that focus on all aspects of valve performance and quality-of-life indicators. Each arm of the trial contains a sufficient number of patients to support independent statistical analysis, according to Edwards.

Wood said the company designed the trial to essentially be two trials in one because the control groups in the two study arms are very different – one control group will be receiving medication as treatment for aortic stenosis while the other control group undergoes open-heart surgery.

Because each arm of the trial is powered individually, Wood said that if one arm enrolls patients much faster than the other Edwards could take that arm and pursue approval for that indication first.

According to Larry Biegelsen, a device analyst with Prudential Equity Group, the trial design is consistent with the company's prior statements.

"We believe that approval to initiate the trial is a positive development and that the two separate arms of the study [surgical and non-surgical] provide [Edwards] with two 'shots on goal' that enhance the trial's chance for a successful outcome," Biegelsen wrote in a research report.

Also in the report, Biegelsen wrote that, "we believe the non-surgical arm has the highest likelihood of success partly because crossover from medical management to the transcatheter arm is not allowed for one year."

The Edwards Sapien transcatheter aortic heart valve integrates balloon-expandable stent technology with a replacement tissue heart valve. The Sapien valve is compressed onto the balloon to about the diameter of a pencil and is threaded through the patient's circulatory system from either the leg or it is inserted between the ribs and expanded directly over the aortic valve. The therapy was originally developed in conjunction with Alain Cribier, MD, chief of cardiology at the University Hospital (Rouen, France), who performed the first transcatheter valve replacement in April 2002, the company said.

Wood said the company expects to receive European approval by the end of the year. He estimated that Edwards could begin marketing the device in the U.S. by 2010, which assumes 12 to 18 months for enrollment, one year for follow-up and one year for regulatory review.

In the trial, patients will be defined as "high-risk" based on a combination of their risk factors — such as their age, whether or not they have had a previous open-heart surgery – and the clinican's judgment, Wood said.

Edwards will start enrolling patients at two initial study sites: New York-Presbyterian/Columbia University Medical Center (New York) and the Cleveland Clinic Foundation (Cleveland). Both sites were part of the company's earlier transfemoral feasibility study. Before expanding to 15 U.S. study sites, Edwards needs to submit additional follow-up data from the original 55-patient feasibility study.

"While the FDA has agreed with the trial design, we are initially limited to eight sites and 40 patients until FDA reviews additional data from our U.S. feasibility trial which we plan to submit in the next 30 days," Wood explained Tuesday in a conference call to discuss the trial.

"Clearly we're very excited to begin this landmark trial and to be working with leading clinicians to bring the Sapia valve to market," said Michael Mussallem, CEO and chairman of Edwards during the call. "While surgery remains an excellent therapy for patients suffering from aortic stenosis, there is a large group of patients that remains untreated … ."

Initially, clinicians in PARTNER will deliver the Sapien valve using Edwards' RetroFlex transfemoral delivery system by making a small incision in the person's groin and threading the catheter up through the femoral artery. In the third quarter of this year, the company hopes to add its Ascendra transapical delivery system to the trial, which delivers the valve by surgically inserting it between the patient's ribs and entering through the bottom part of the heart.

"We have developed one valve with two approaches," Wood said, emphasizing that the trial is intended to evaluate the valve performance rather than the delivery system. "At the end of the day how you deliver the valve is less important than the valve itself."

The transfemoral approach is performed in a cath lab by an interventional cardiologist, whereas the transapical procedure is performed in the operating room with a cardiac surgeon, Wood said. He said the "partnership" between the interventional cardiologist and the surgeon is one rationale for the trial's title.

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