CDU Washington Editor

GAITHERSBURG, Maryland — In early March, the cardiovascular panel of the FDA’s Center for Devices and Radiological Health examined — and by a 9-2 vote recommended against — the application for the Chronicle implantable hemodynamic monitoring system, from Medtronic (Minneapolis). An issue troubling the panel was the systems’s failure to meet a primary study endpoint — reduction of patient trips to the hospital.

While praising the study design, the company’s presentation and the device’s purpose, panelists also noted the Chronicle was presented as therapeutic device and suggested it would have been better presented as a diagnostic.

Implanted in the chest and about the size of a pacemaker, the Chronicle monitors the right ventricle to gauge intra-cardiac pressure in patients with heart failure by means of a lead inserted into the heart. It is one of a new wave of home monitoring systems pushing into the marketplace that use either the Internet or standard telephone line transmissions to deliver data to doctors.

In the company’s Phase III study — the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial — all 274 subjects received the study device, with data from the control subjects withheld from clinicians for six months.

Randall Brockman, MD, a medical officer at FDA’s Office of Device Evaluation, told the panel that “while there was a trend toward the primary endpoint of a reduction in overall heart failure hospital equivalents in the Chronicle group, it was not statistically significant.” In the first six months, 72 of the reporting patients had to go to the hospital, compared with 99 in the subjects who did not report their data.

When combined with several other measures of reports of care episodes, the reporting group enjoyed an event rate just 21% lower than the controls, a P score of .33, falling short of statistical significance.

The Chronicle did well on the primary safety objective, zero device-related complications at six months for 80% of subjects, attained this number easily by ringing in at zero events for 91.5% of the enrollees. The secondary safety endpoint, freedom from pressure-sensor failure at six months for nine of 10 patients, likewise was met easily as none of the leads failed at the half-year interval.

Panel member Jeffrey Borer, MD, a professor of cardiovascular medicine at Weill Cornell University Hospital (Ithaca, New York) gave the panel a brief review of the application, and described the device as a “very complicated but very ingenious tour de force.”

Borer said that in the first phase trial, the Chronicle was compared to the Swan-Ganz catheter, used only in a clinical setting, and that the Chronicle “showed relatively good equivalence” for data collection. The Phase II study evaluated durability and safety in 148 patients who were followed for periods as long as 73 months. Some adverse events surface in this phase, but “after some manufacturing flaws were resolved,” the agency deemed these fixes to be appropriate, Borer said.

The enrollees all fell into either Class III or IV in the New York Heart Association (NYHA) scale, and those in the IV class, profoundly ill and usually confined to bed, were more likely to show up in the hospital if their data sets were filed with their doctors.

Borer noted “a number of unanswered questions” but said the Chronicle “is certainly a great research tool” because “we would learn a tremendous amount,” from its use.

John Teerlink, MD, the director of the heart failure clinic at the San Francisco Veterans Affairs Medical Center (California), said, “as a heart clinician, the benefit [of the device] is so tantalizing, I really want this to work.” But he noted risks that included potential device-related complications, and “opportunity cost” in the form “of real estate on the chest,” a reference to loss of space available in the body for pacemaker or defibrillator implant.

David Steinhaus, MD, Medtronic chief medical officer, in a statement said that while the company recognized that the Compass-HF trial had not met its primary endpoint, the company stood by the benefits of the technology and will develop “the appropriate path for approval.”