A Clinical Trial of Progesterone for Severe Traumatic Brain Injury

LanAnh Ngo, Mercer University College of Pharmacy 2015

Progesterone is commonly known as a female reproductive hormone, but studies have shown its pleotropic properties as a neuroprotective agent.1 The use of progesterone in traumatic brain injury has been studied to take advantage of this property and possibly for application into clinical practice.

Title: A Clinical Trial of Progesterone for Severe Traumatic Brain Injury2
Design Multinational placebo-controlled trial with 1195 patients ages 16 to 70 years of age with severe traumatic Brain Injury (TBI)
Objective The study aimed to investigate the efficacy and safety of progesterone in a large prospective, phase 3 trial.
Study groups Randomly assigned to received progesterone
Methods Patients with severe TBI (Glasgow Coma Scale score ≤ 8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone (n = 591) or placebo (n = 588). Dosing began within eight hours after injury and continued for 120 hours beginning with a loading dose of 0.71 mg/kg/hour for one hour followed by 0.50 mg/kg/hour for 119 hours. The two follow up visits were 90 and 180 days after injury.
Duration 6 months
Baseline Characteristics Glasgow Coma Scale overall score and motor score, Marshall classification, and pupillary reactivity were similar in the two groups.
Results Of the 1195 patients that undergone randomization, 1179 patients were included in the analysis. The outcome of the primary efficacy analysis showed 22.2% either dead or in vegetative state, 27.4% with severe disability, 18.4% with moderate disability, and 32% with good recovery.
Adverse Events Common Adverse Events: Common Adverse Events: blood or lymphatic disorder (32.6%), cardiac disorder (22.3%), endocrine disorder (7.4%), gastrointestinal disorder (30.9%), infection or infestation (65.3%), nervous system disorder (44.6%)
Serious Adverse Events: Not reported
Percentage that Discontinued due to Adverse Evens: Not reported
Study Author Conclusions Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI.

Due to the nature of the injury, its complexity, and differences in patient response to the injury, a use of a single agent for treatment may be difficult as shown in this study. The use of progesterone as an adjunct to other therapies may be more appropriate. This study alone should not disregard the use of progesterone in traumatic brain injury and future studies should aim to see the effects of progesterone along with other therapies that have shown to have better outcomes for the treatment of TBI.

References:

  1. Wei J and Xiao G. The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects. Acta Pharmacologica Sinica 2013; 34: 1485–1490. http://www.nature.com/aps/journal/v34/n12/full/aps2013160a.html
  2. Skolnick B, Maas A, Narayan R, van der Hoop R, MacAllister T, Ward J, et al. A Clinical Trial of Progesterone for Severe Traumatic Brain Injury. N Eng J Med 2014; 371: 2467-76.
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