The Neurological Devices Panel (the Panel) met on Thursday, November 16, 2000 to make recommendations to the Food and Drug Administration (FDA) on the design of clinical trials for endovascular devices to treat and prevent acute ischemic stroke and for endovascular devices to provide hypothermia neurological protection.
Fourteen representatives from the public, professional societies, and industry presented their views and helpful information on the design of clinical trials for these types of devices to the Panel. Two Panel members, both Center for Drug Evaluation and Research Advisory Committee consultants, gave background presentations at the beginning of the Panel’s deliberations. After discussion of the information presented to them, the Panel considered the FDA questions and provided their recommendations.
The FDA questions on treatment and prevention of ischemic stroke addressed the following issues: 1) inclusion criteria and special patient cohorts, 2) appropriate control populations, 3) primary and secondary safety and effectiveness outcomes, 4) possible bias and confounding factors, and 5) patient outcome evaluation and follow-up times.
The Panel made helpful recommendations on the design of clinical trials for endovascular devices to treat and prevent acute ischemic stroke. They recommended that lessons learned from drug trials be utilized in the design of device clinical trials. Concerning patient selection, the Panel recommended including symptomatic patients in stroke treatment studies using a randomized concurrent control design. The control group would depend on the time since the onset of stroke symptoms. The control population for stroke prevention studies could be best medical therapy. They identified the following safety outcomes: perforation injury, infection, reocclusion, recurrent stroke, and death. For acute stroke treatment trials, the Panel recommended two primary effectiveness outcome measures, both clinical improvement and recanalization. The Panel believed that angiographic findings alone would be insufficient to assess the safety and effectiveness of these devices. For stroke treatment studies, the Panel thought that effectiveness should be evaluated 24 hours after the initial event and that patients should be followed for at least 3 months. For prevention of stroke trials, follow-up should be for at least 1-2 years.
The FDA questions on hypothermia neurological protection clinical trials addressed the following issues: 1) hypothermia safety parameters (target temperatures, hypothermia duration, and cooling and rewarming rates); 2) temperature monitoring sites and methods; and 3) indication-specific clinical trial design issues for the treatment of cardiac arrest, head trauma, stroke, and aneurysms. These indication-specific design issues included inclusion/exclusion criteria, control populations, safety parameters, outcome measures, evaluation and follow-up times, and special considerations for pediatric and head trauma patients
The Panel commented that cardiac arrest, head trauma, stroke, and aneurysms are life-threatening conditions for which the treatments now available are limited. The Panel made useful recommendations for endovascular hypothermia neuroprotection device trials. They recommended target temperatures of 33 to 35 degrees C; rapid cooling; slow, controlled rewarming; temperature monitoring at the pulmonary artery or urinary bladder; broad inclusion criteria; and psychometric effectiveness evaluation. They thought that follow-up times could be less than 3 months. For stroke trials, the design could include a placebo treatment after the window of tissue plasminogen activator (tPA) treatment effectiveness was past. The Panel noted that trauma is a leading cause of death of pediatric patients.
The Panel membership for this meeting consisted of three neurosurgeons, six neurologists, two interventional radiologists, a biomedical engineer, a consumer representative, and an industry representative.
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