FDA Advisory Committee Rejects AngelMed Guardian Intracardiac Monitor

After extensive discussions about problems with the pivotal trial, members of the US Food and Drug Administration’s Circulatory Systems Devices panel unanimously lined up against an implantable intracardiac device intended to prompt patients with signs of coronary occlusion to seek medical care immediately.

Although four of the 12 panelists said there was reasonable assurance that the device was safe, all came down against it in terms of efficacy or the risk-benefit balance.

The AngelMed Guardian system (Angel Medical Systems; Shrewsbury, NJ) is designed to alert patients to ST-segment shifts indicative of coronary artery occlusion with vibratory, auditory, and visual warnings. It consists of an implantable intracardiac monitor, an external device that manages alerts, and a programmer that can retrieve and display data from the implanted device.

The company is seeking approval based on the ALERTS study, which randomized 907 patients at high risk for MI—all of whom had the device implanted—to have alerts turned on or off for 6 months. Included patients were at high risk for MI.

The primary safety objective of the study—to have at least 90% of patients free from system-related complications at 6 months—was met (96.7%). However, the primary efficacy outcome—a composite of cardiac death or unexplained death, new Q-wave MI, or time to arrival at a medical facility for a confirmed occlusive event greater than 2 hours—was not.

Interpretation of the trial findings was complicated, according to both FDA reviewers and the panelists, by several trial conduct issues:

• The trial was halted prematurely because of incomplete and unreliable ECG data, a move the FDA called a significant protocol violation.
• Adjudication of certain events went against protocol.
• Multiple “look-back” windows were used to determine whether a clinical event was preceded by changes detected on the intracardiac monitor without proper adjustment.
• There was a post-hoc change from using a single ECG at baseline to determine the development of new Q-waves to using dual ECGs at baseline.

Those issues made it difficult for panelists to get a good sense of whether the device actually had any clinical impact, which tilted the risk-benefit balance into unfavorable territory.

Nevertheless, several panelists expressed a desire for development of the device to continue.

“If efficacy were improved, the hazard associated with the device would be justifiable,” panelist John Hirshfeld Jr., MD (University of Pennsylvania), said after the voting was complete. “I do hope the sponsor continues to develop and refine this device to improve detection because I think that there is a tremendous unmet need.”

Jeffrey Brinker, MD (Johns Hopkins Hospital, Baltimore, MD), agreed.

“The technology is exceedingly interesting . . . and it’s evolved to a point of, I think, utility,” he said. “I think we need a better arrangement of data and more data, but I think this is a potentially useful device.”

Related Stories:

• Implantable Device Offers Feasible Way to Monitor ST-Segment Shifts