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WASHINGTON -- Although results from the CHAMPION trial of an implanted pulmonary artery monitor for patients with heart failure were hailed as a major breakthrough last year, FDA reviewers are questioning the clinical significance of the study's endpoint.
In briefing documents prepared for an FDA advisory committee meeting slated for Thursday, the FDA reviewers said CardioMEMS Champion HF Monitoring system demonstrated only a scant absolute risk reduction of 0.12 heart failure-related hospitalization events per patient per six months, illustrating how a blockbuster finding can be turned into a ho-hum result when data are reinterpreted.
When the CHAMPION findings were reported in May 2010 at the Heart Failure Congress in Berlin, William T. Abraham, MD, of Ohio State University, trumpeted the finding that, after six months, there were 83 hospitalizations for heart failure among the 270 patients randomized to treatment guided by hemodynamic measurements from the CardioMems Heart Sensor, compared with 120 heart failure hospitalizations in the 280-patient control arm, which Abraham said represented 38% annualized relative risk reduction.
Treating only four patients for a year would reduce heart failure hospitalizations by one, Abraham added.
In data submitted to the FDA by device-maker CardioMEMS of Atlanta, the hospitalizations went from 83 to 84 and the FDA reviewers said eight patients would need to be treated in order to prevent one heart failure hospitalization.
The device, a wireless, battery-less, radiofrequency activated system, is about the size of a paper clip and it can be implanted in either the right or left pulmonary artery branch, provided the artery has an average lumen of 10 mm.
The device "has an average implant time of seven minutes after catheterization," Abraham said.
When the patient places a wand-like device over the implant area it activates the radiofrequency signal in the implanted monitor, which sends pulmonary pressure readings to the physician's office.
If approved, the CardioMEMS Champion HF Monitoring system would be the first permanently implanted device to monitor patients with advanced heart failure.
In addition to having fewer hospitalizations, the patients with monitors had shorter hospital stays -- roughly 1.6 fewer days in hospital than controls.
Panelists at Thursday's meeting will be asked to discuss the significance of those several days.
Patients with the monitoring system also reported higher quality-of-life scores.
The rates of death were similar between the two arms of the study.
The FDA also raised concerns about the conduct of the study.
CardioMEMS nurses and investigators were aware of which patients were in which group and made treatment recommendations to doctors at investigational site for patients who had the device. FDA is concerned that, by making heart failure recommendations only to the treatment arm, the results may be biased because the recommendations could keep those patients out of the hospital, with no comparable way to keep the control arm patients out of the hospital.
"Additionally, the FDA is concerned that the level of involvement of the sponsor during the clinical trial would not be duplicated in a post-market environment," FDA reviewers wrote.
They added that the "FDA has not provided to date any evidence from the study to support a finding that either inappropriate contact was made with study site personnel or that legitimate contact with study site personnel, as outlined in the protocol, resulted in bias being introduced into the study results obtained."