The pharmacologic management of acute spinal cord injury in humans remains equivocal despite decades of animal and clinical investigation. The National Acute Spinal Cord Injury Study (NASCIS) was established in 1977 to evaluate new treatment modalities using a multi-center randomized clinical trial (RCT) methodology. The first RCT (NASCIS I) was successfully completed in 1983. This application is for the continuation of NASCIS II, a randomized clinical trial which is testing the efficacy and safety of a high dose Methylprednisolone (30mg/K bolus and 5.4 mg/K/hr maintenance dose for 23 hours) or Naloxone (5.4 mg/K bolus and 4.0 mg/K/hr maintenance dose for 23 hours) regimen compared with placebo. Ten acute spinal cord injury studies are participating in the trial which requires 480 patients to document clinically significant changes in neurologic function. The monthly accrual of patients has averaged 11.2 rather than the predicted 13.5 and a further two years of study is required to complete patient intake into the study and complete all the one year follow-up neurological examinations. Patients must have been injured within 12 hours of admission to the Center to be eligible for the study. The 12 hour criterion, which relates the RCT to the experimental literature, was previously planned to be 18 hours and accounts for some reduction in patient accrual. Using standard protocols and procedures, neurological examinations are performed on patients in the ER, at 24, 48 and 72 hours after injury, as well as at six weeks, six months and one year after injury. The principal outcome measures are documented changes in motor function, and in pinprick touch and deep pain sensation. The study is continuously monitored for unusually high complication and mortality rates and intermittently analyzed for greater than anticipated treatment effects. NASCIS is the only established RCT network for the clinical evaluation of treatment maneuvers for acute spinal cord injury. A lack of treatment effect from the two drug regimens currently being studied would prevent costly and unnecessary treatment of patients and would directly influence much of the experimental work conducted or being planned in this area. The demonstration of a beneficial effect from either of the two drug protocols would profoundly influence the treatment of acute spinal cord injury.
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