Neuropsychological rehabilitation for traumatic brain injury: do carers benefit? Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial.
This study evaluated the effectiveness of a new rehabilitation service, compared with existing services, for carers of people with traumatic brain injury (TBI). Subjects were 96 adult carers of people consecutively admitted to two local hospitals. They were assigned to one of three groups: Early new service (pre-discharge); Late new service (post-discharge); or a Control condition (existing services only). Individual randomization was not possible and randomization by hospital site was rejected because of demographic and clinical differences between sites. Group assignment was determined by a pre-specified timetable which alternated between hospitals. Two outcomes were compared at 6 months post-injury: carers' emotional distress and how well-informed they felt about TBI and available resources. Analyses adjusting for potential confounding factors confirmed a clinically plausible superior outcome for both intervention groups compared to the control group. However, these differences did not obtain statistical significance (p > or = 0.01). Several reasons for these findings are discussed, including the novelty of the new service and methodological issues such as statistical power. Longer term follow-up studies are required as psychological sequelae and, therefore, the need for intervention is known to increase with time and may not be most apparent during the first 6 months. Severe traumatic brain injury (TBI) has been increasing with greater incidence of injuries from traffic or sporting accidents. Although there are a number of animal models of TBI using progesterone for head injury, the effects of progesterone on neurologic outcome of acute TBI patients remain unclear. The aim of the present clinical study was to assess the longer-term efficacy of progesterone on the improvement in neurologic outcome of patients with acute severe TBI.
                A total of 159 patients who arrived within 8 hours of injury with a Glasgow Coma Score </= 8 were enrolled in the study. A prospective, randomized, placebo-controlled trial of progesterone was conducted in the Neurotrauma Center of our teaching hospital. The patients were randomized to receive either progesterone or placebo. The primary endpoint was the Glasgow Outcome Scale score 3 months after brain injury. Secondary efficacy endpoints included the modified Functional Independence Measure score and mortality. In a follow-up protocol at 6 months, the Glasgow Outcome Scale and the modified Functional Independence Measure scores were again determined.
                Of the 159 patients randomized, 82 received progesterone and 77 received placebo. The demographic characteristics, the mechanism of injury, and the time of treatment were compared for the two groups. After 3 months and 6 months of treatment, the dichotomized Glasgow Outcome Scale score analysis exhibited more favorable outcomes among the patients who were given progesterone compared with the control individuals (P = 0.034 and P = 0.048, respectively). The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). The mean intracranial pressure values 72 hours and 7 days after injury were lower in the progesterone group than in the placebo group, but there was no statistical significance between the two groups (P > 0.05). Instances of complications and adverse events associated with the administration of progesterone were not found.
                Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug.
                ACTRN12607000545460.
There is no reliable evidence from randomised controlled trials to support the effectiveness of haemostatic drugs in reducing mortality or disability in patients with TBI. New randomised controlled trials assessing the effects of haemostatic drugs in TBI patients should be conducted. These trials should be large enough to detect clinically plausible treatment effects.