Medical Device Daily Associate

Circulatory support system maker WorldHeart (Oakland, California) got a very early Christmas present this week in the form of a clinical trial patient enrollment reduction, which the company said could significantly reduce the time required to complete its Randomized Evaluation of the Novacor LVAS In A Non-Transplant Population (RELIANT) trial for use of the its Novacor left ventricular assist system as a destination therapy (DT).

The FDA has given conditional approval of the company's investigational device exemption (IDE) supplement for modifications to the trial, including a reduction in sample size, from 390 to 208 patients.

“This reduction in the required sample size by almost a factor of two will obviously have a pretty significant impact on the duration of the trial,“ said Jal Jassawalla, president and CEO of WorldHeart during a conference call on the conditional approval, though he declined to say exactly how much of a reduction in trial time the IDE might provide.

He added that the rate of implant would also increase as the number of centers involved in the trial continued to increase. “We eventually expect to get to 30 to 35 centers and we're currently at about 20 centers.“

The RELIANT trial, first unveiled in November 2003, has already enrolled nearly 20% of the newly required number.

The company said the rate of patient enrollment has been increasing and is expected to accelerate as new centers complete the enrollment process and, it noted, the enrollment rate in 1Q06 was double the enrollment rate in the prior quarter.

The trial is designed to evaluate the Novacor for DT use by patients suffering from irreversible left ventricular failure who are not candidates for transplantation. Recipients are being randomized, on a 2:1 basis, to receive the Novacor or Thoratec 's (Pleasanton, California) HeartMate XVE LVAS. The goal of the trial is to show equivalency to the HeartMate XVE, which received a DT approval in April 2003 (Medical Device Daily, April 3, 2003).

The FDA also expanded the inclusion criteria for the trial to include patients in New York Heart Association (NYHA) Class IIIB heart failure, as well as currently included NYHA Class IV patients.

The company said that this patient class expansion is also expected to yield a “significant increase in the patient enrollment rate,“ further accelerating completion of the trial. . . . This is in recognition of advances in the field of mechanical [heart] support and recognition that these devices are now appropriate to use in a broader range of patients, not just those in eminent risk of death.“

The Novacor is also now available, within the trial, to DT patients requiring replacement of a failed HeartMate XVE originally implanted outside of the study.

“These trial revisions reflect advances in the field of mechanical circulatory support, allowing us to expand the trial to a broader group of patients more quickly,“ said John O'Connell, MD, a cardiologist and director of the Center for Heart Failure at the Bluhm Cardiovascular Institute and professor of medicine at the Feinberg School of Medicine, Northwestern University (both Chicago). “It is encouraging to see the FDA adopt trial approaches that maintain scientific rigor, are significantly more timely and have the potential to bring important new technologies and therapies to patients.“

Under the newly approved IDE supplement, the primary endpoint for the trial – formerly only patient survival – is now a composite of patient survival, device replacement and neurologic events. The use of a composite primary endpoint accounted for the required patient enrollment. Secondary endpoints include quality of life, adverse events and cost effectiveness.

The broadened patient inclusion criteria also include reduction of the total time of heart failure exposure from 60 out of 90 days to 30 out of 60 days, and the early identification of patients at risk. The company said that the added patient cohort allows DT patients currently supported by the HeartMate XVE in need of device replacement to electively receive the Novacor system.

Thus far, 38 patients have been enrolled in the study, and these patients will count towards the required enrollment of 208, upon confirmation of poolability.

The FDA approval of the revised study is conditional upon submission of additional details related to the study's statistical model, the incorporation of additional secondary analyses in the study protocol, and adjustment of the composition of the clinical events review committee.

“We are extremely pleased with the collaborative process between the FDA, the RELIANT trial clinical executive committee and WorldHeart, which led to the revised study design,“ said Jassawalla. “These changes to the RELIANT trial were driven by the experience of leading cardiologists and cardiac surgeons in delivering mechanical circulatory support solutions to their patients.“

Jassawalla said that after the trial is completed, WorldHeart expects to make a pulsatile ventricular assist devices (VAD) available to clinicians “which we believe will drive adoption in the destination therapy market.“

Last month (MDD, March 28, 2006), the company reported the first human implant of its rotary VAD at St. Luke's Hospital (Thessaloniki, Greece). The procedure marked the start of the company's first-in-man feasibility study of this advanced-generation device. Additionally, he said that the company's next-generation pulsatile pump, the Novacor II, has begun chronic animal trials.

He said that the company believes that there is a spectrum of heart failure, “and as we gain experience in this field we learn that there is not a one size solution that is optimal for all patient needs.“

As the only company with both rotary and pulsatile next-generation VADs under development, WorldHeart makes the claim that it is currently the VAD manufacturer best able to address the full spectrum of patient needs, from partial support to full functional support.

The Novacor LVAS is commercially approved as a bridge to transplantation in the U.S. and Canada.

In Europe, the device has unrestricted approval for use as a bridge to transplantation, an alternative to transplantation and to support patients who may have an ability to recover the use of their natural heart.

In Japan, the device is approved for use in cardiac patients at risk of imminent death from non-reversible left ventricular failure for which there is no alternative except heart transplantation.

WorldHeart also yesterday reported that it has satisfied Nasdaq's minimum bid price requirement of being at or above $1 a share for its common stock for more than 10 consecutive business days, regaining compliance prior to the previously announced deadline of May 30.