GAITHERSBURG, MD. — A federal advisory panel recommended against approval of an implantable device that continuously measures intracardiac pressures in ambulatory patients with moderate to advanced heart failure, but panel members were enthusiastic about its potential and urged the manufacturer to continue studying the device.
At a meeting last month, the Food and Drug Administration's Circulatory System Devices Panel voted 9–2 that the Chronicle Implantable Hemodynamic Monitoring (IHM) System was “nonapprovable.”
The manufacturer, Medtronic, had proposed that it be approved for the chronic management of patients with moderate to advanced heart failure in New York Heart Association class III or IV to reduce hospitalizations for worsening heart failure in these patients.
Although panelists generally agreed that intuitively, the technology made sense and provided useful information, they voted against approval because the COMPASS-HF study, the clinical trial submitted for approval, did not meet the primary effectiveness end point of showing that it reduced the rate of heart failure hospitalization equivalents (HF-related hospitalizations, HF-related emergency department or urgent-clinic visits requiring intravenous therapy) in patients with NYHA III or IV heart failure. And while the study provided reasonable assurance that the device was safe, panelists also cited the potential risks of an implantable device, with no effectiveness data to counterbalance the potential risks.
Panelist Dr. John Teerlink, director of heart failure at San Francisco Veterans Affairs Medical Center, described the technology as “tantalizing,” but said that there was no evidence that it reduced patient hospitalizations for worsening heart failure.
This is a “lifelong implant, with certain known risks” and unknown risks that may occur with time, said panelist Dr. Jeffrey Borer, head of the division of cardiovascular pathophysiology, at the New York-Presbyterian Hospital. While he believed that the device accurately measured pressures that he believed were physically and pathophysiologically relevant.
“I haven't seen the data that tell me how to apply this information for predictable clinical benefit,” Dr. Borer said.
The two panelists favoring approval thought that the device could be approved, but restricted to a very select population of heart failure patients.
The Chronicle IHM system includes the hemodynamic monitor, the size and shape of a pacemaker, that is implanted into the upper chest, with a pressure sensing lead that is inserted into the right ventricle.
The system measures and stores data on right ventricular systolic and diastolic pressures, and estimated pulmonary artery diastolic pressure, as well as heart rate, core temperature, and patient activity, information that is transmitted by the patient remotely to the clinician, who can access the data via a Web site.
The COMPASS HF multicenter study enrolled 274 patients with NYHA class III (84%–87% of the patients) or IV heart failure, whose mean age was 58, who had been on standard medical therapy for at least 3 months, and had at least one HF-related hospitalization or emergency department visit that required intravenous treatment within the previous 6 months. The device was implanted in all patients, but clinicians had no access to the information in 140 patients, who served as the controls.
The rate of heart failure hospitalization equivalents through 6 months, the primary effectiveness end point, was 21% lower in the Chronicle arm, which was not statistically significant: 44 patients in the Chronicle arm had 84 HF-related hospitalization equivalents, (an event rate of 0.67 over 6 months), compared with 60 patients in the control group who had 113 HF-related events, an event rate of 0.85. Events in both groups were mostly hospitalizations.
Clinicians made nearly three times as many adjustments of medications in the CHRONICLE patients, with no evidence of complications associated with overdiuresis, according to Medtronic.
The panel agreed there was reasonable assurance that the device was safe. Almost 92% of patients had no system-related complications over 6 months, and there were no cases of pressure sensor failures.
Of the 277 attempted implants (3 were not successful), there were 24 complications in 23 patients, most frequently lead dislodgement.
Panelists encouraged Medtronic to continue studying the device.
The FDA usually follows the recommendations of its expert advisory panels, which are not binding. In a statement issued after the meeting, Dr. David Steinhaus, medical director of cardiac disease management at Medtronic, said that the company was committed to making the Chronicle IHM available worldwide to heart failure patients and plans to work closely with the FDA to “define the appropriate path for approval.”