FDA Advisory Panel Says More Data Needed for Supersaturated Blood Device in AMI Patients

Shelley Wood

March 24, 2009

Gaithersburg, MD - The FDA Circulatory System Devices Panel voted nine to five against recommending approval of a device designed to delivery supersaturated oxygen therapy after PCI, with the aim of reducing final infarct size. Panelists who tipped the vote toward the "no" majority were concerned that the TherOx Aqueous Oxygen System (Therox, Irvine, CA), which combines a patient's own blood with supersaturated oxygen and then delivers it to the injured area of the myocardium, showed some worrying trends toward increased adverse events.

As previously reported by heartwire , the TherOx device was originally tested in the AMIHOT trial, where it failed to show a difference in infarct size or clinical events at 30 days for the trial as a whole but hinted that a subgroup of patients might benefit. In the subsequent AMIHOT II trial, also reported by heartwire , researchers found that the supersaturated blood might be beneficial in patients with large infarcts after acute MI who ended up undergoing PCI (and received the supersaturated blood) within six hours of symptoms. In AMIHOT II, reduction in infarct size measured by Tc-99m sestamibi single photon emission computed tomography (SPECT) at 14 days--the primary end point of the trial--was significantly greater among patients who underwent supersaturated oxygen therapy. After treatment, patients who received their own, supersaturated blood had an infarct size that was 6.5% smaller than patients who received standard therapy. The proportion of patients with immeasurable infarcts at 14 days was also significantly different between the two groups.

MACE, however, actually trended higher in the supersaturated-blood group in AMIHOT II, and this was one of the findings that worried panelists who voted against approval. Moreover, the relatively meager difference in infarct size reduction seen between the treated and control groups (a 3.9% mean, 6.9% median absolute difference), from a pooled analysis of AMIHOT I and II data, did not seem large enough to justify the uncertainty about adverse effects, panel members said.

In discussing the reasons why the device should not be approved at this time, panel members called for preclinical data to help understand the mechanism of benefit; more precise safety data, rather than a combined MACE end point; and more clinically meaningful end points, rather than a surrogate end point (infarct size) as the primary effectiveness end point.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.



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