Treatment of patients with severe head injury by triamcinolone: a prospective, controlled multicenter clinical trial of 396 cases

Abstract

The present studies were conducted to test whether the outcome of severe head injury is improved by early administration of the synthetic corticosteroid triamcinolone. In a prospective, double-blind, multicenter clinical trial, 396 patients with severe head injury were randomized to a steroid group (n = 187) receiving 200 mg triamcinolone acetonide (Volon A soluble) i.v. within 4 h after trauma, followed by 3 x 40 mg/day i.v. for 4 days, and 3 x 20 mg/day i.v. for a further 4 days, and a placebo group (n = 209) receiving injections which did not contain any active drug. The placebo group was subjected to the same standard treatment procedures. Clinical features were not different between the groups upon admission to hospital. Subdural hematoma, epidural hematoma, and focal supratentorial contusion were among the most frequent diagnoses. The result of treatment with triamcinolone was assessed at discharge from the hospital and at 1 year after trauma, using the Glasgow Outcome Scale. Differences in favor of steroid treatment could be detected with regard to the patients' condition at discharge (P = 0.0634). More patients with steroids had a good recovery (49.2% vs 40.7%), and fewer died (16.0% vs 21.5%). Differences in outcome were even more pronounced (P < 0.0145) in patients with a focal lesion and a Glasgow Coma Score on admission of < 8 (n = 93). In this group, 34.8% of the patients made a good recovery, as against 21.3% of the placebo group; mortality was also lower in the verum group (19.6% vs 38.3%). The results indicate that a major subgroup of patients with severe head injury benefits from early administration of triamcinolone. Efficacy of the treatment can be expected, in particular, in patients with a focal cerebral lesion and a Glasgow Coma Score of < 8 on admission. Administration of steroids beginning at the scene of an accident would therefore be beneficial in these cases.

Novel Pharmacologic Strategies in the Treatment of Experimental Traumatic Brain Injury: 1998

“…Gianotta et al (1984) reported that high-dose methylprednisolone (30 mg/kg) significantly reduced mortality in severely head-injured patients. In a multicenter trial conducted in Germany, treatment of severely head-injured patients with the synthetic corticosteroid triamcinolone significantly reduced mortality and improved long-term neurological outcome (Grumme et al, 1995). Further evaluation of these compounds in valid, clinically relevant animal models and continued clinical testing appear to be warranted.…”

Clinical Trials in Traumatic Brain Injury: Past Experience and Current Developments

“…19 In the triamcinolone trial, a 5% increase in good recovery was observed in patients on active treatment. 20 In the polyethylene glycol-conjugated bovine superoxide dismutase (PEGSOD) trial, there was a 9% improvement in favorable outcome noted. 21 In the Bradycor trial there was a 12% improvement.…”

Critical appraisal of neuroprotection trials in head injury: What have we learned?

“…Specific lessons, however, have been learned from previous attempts and general principles can be suggested: 1) better understanding of the pathophysiology of head injury both severe and moderate is imperative, and the mechanism should be demonstrated in both animal models and human TBI; 2) better translational processes are very important to design therapeutic interventions that have relevance to the clinical practice, brain tissue penetration and pharmacokinetics in human TBI should be carefully considered and investigated, safety data should include interactions with other agents, and the possibility of multiple agent treatment should be explored; 3) the appropriate therapeutic time-window should be identified and dynamic processes should be developed to allow individual patient adjustments, e.g., giving the trial medication at the site of the accident; 4) as a result of the above, specific consideration of the actual consent procedure and serious thought should be given to the concept of waived consent for trials in head injury; 5) proper patient selection is necessary, which will expose to treatment those patients that will benefit most from any potential intervention; 6) identification of an appropriate surrogate endpoint is highly desirable, but it has to be fully validated before it can be applied; 7) careful statistical evaluation before and during any trial will ensure avoidance of pitfalls in recruitment and analysis; protocol adherence and center monitoring is important in establishing internal validity and smoothing out the significant variability in treatment, and 8) full publication of the results of any trial, irrespective of the outcome, is imperative for all investigators to scrutinize the data and draw appropriate conclusions as early as possible. [71][72][73][74][75][76][77][78][79] …”