The Circulatory System Devices Panel (the Panel) met on Thursday, March 17, 2005 in Gaithersburg, Maryland, to review the information in a premarket notification (510(k)) submission for the Alsius Corporation CoolGard 3000/Alsius Icy Heat Exchanger Catheter Thermal Regulating System, K040429. The device is intended for use in the induction, maintenance and reversal of mild hypothermia in the treatment of unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest when the initial rhythm was ventricular fibrillation (VF).
The meeting was called to order by Dr. Maisel, Chairman, and two public speakers were recognized. The sponsor then gave a presentation which included a discussion of the features of their device, the ILCOR (International Liaison Committee on Resuscitation) Recommendations on Hypothermia in Post-Cardiac Arrest Patients and their clinical data. The data included a summary of the U.S. feasibility study, a meta-analysis of three published articles on surface cooling and data from their “AKH” registry in which their device was used. Their presentation also included a brief discussion of the CPC (Cerebral Performance Categories) Scale used as a clinical assessment endpoint.
The FDA presentation followed and included a brief summary of the indications for use earlier granted for the subject device, a clinical and statistical review of the meta-analysis and AKH data, and an explanation of the CPC Scale. This was followed by Panel member presentations by Drs. Somberg and Brott) and a full Panel discussion.
The Panel then considered FDA’s five questions. These questions addressed: 1) the safety of the device; 2) the effectiveness of the device; 3) the adequacy of the data to support a acceptable risk/benefit ratio; 4) if the risk/benefit is ratio is acceptable, what would be adequate labeling and is a postmarket study necessary; and 5) if the risk/benefit ratio is not acceptable, what type and amount of information would be necessary to provide an acceptable risk/benefit ratio.
Q1. The Panel was in general agreement that there was insufficient safety data was presented by the sponsor to ensure the safety of the endovascular device in this clinical use. Most Panel members expressed that more information would be required including additional data on acute pancreatitis, renal insufficiency, thrombosis, infection/sepsis, recurrent cardiac events, and device mechanical failures. Several Panel members indicated that the most appropriate way to collect this information was through a randomized controlled study (RCT) with surface cooling as the control (treatment).
Q2. The Panel believed that there were difficulties in interpreting the effectiveness data presented by the sponsor and that this was limited by the method in which data were collected (registry study). The Panel also stated that they were not convinced that hypothermia in general was proven to be a beneficial therapy for such patients and results from surface cooling data could not necessarily be applied to endovascular cooling devices/techniques. Again, several Panel members suggested that a RCT was the optimal method of answering the question of effectiveness.
Q3. The Panel was in near consensus that the data provided by the sponsor did not reach an acceptable risk to benefit ratio threshold which would support a marketing clearance, although a couple believed that the data were close and suggested some promise for its use.
Q4. The Panel noted that since they had reached a near-consensus on Question 3 above, that there were no significant specific recommendations regarding labeling changes and a post-market study.
Q5. The Panel felt that additional clinical data would be required to reach a marketing threshold. The Panel suggested that endpoints assessed at 3 or 6 months would be adequate. There was general consensus that a scale such as the CPC scale might be adequate if the patient categories were supported by more objective or detailed inventories of activities of living and quality of life. The Panel also suggested that cognitive endpoints (neuropsychiatric assessments) be included as secondary endpoints. The Panel stated that the collection of safety endpoints as discussed earlier was also vital. The majority of the Panel noted that a RCT would be required to support a marketing application. They suggested a 3-arm study with endovascular cooling, surface cooling, and normothermia, or a 2-arm study with surface cooling as a control. The Panel was in agreement that U.S. sites should be included in any future study and that if foreign sites were used as well, that there be sufficient similarities in “chain of survival” characteristics/times among sites.
The Panel did not vote on a recommendation regarding the determination of substantial equivalence for this 510(k) submission but the consensus of the Panel was that the risk/benefit ratio for the device has yet to be established and that and that additional randomized controlled studies would be necessary.
The Panel membership for this meeting consisted of five cardiologists, two electrophysiologists, two neurologists, a statistician, a consumer representative, and an industry representative.
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