Table 1. Comparison of preclinical and clinical trials of progesterone in TBI.

	Preclinical TBI [180]	Clinical TBI [24, 25, 50, 51]
Injury type	Majority in open head injury with cavity formation (CCI or FPI model) [180]; a few in closed head injury (weight drop model) [181, 182]	Blunt, closed head injury
Injury severity	Mainly moderate, homogenous	Severe only [25, 50] or moderate to severe [24, 51], heterogeneous
Multiple trauma	TBI alone	83% with multiple trauma [50]
Traumatic subarachnoid hemorrhage	Not measured	76%[50]
Age	Mainly young adult	16 to 94 years old, mainly young [24, 25, 50, 51]
Sex	Mainly males	Mixed (male sex, 70-80% )[24, 25, 50, 51]
Initial intervention time	Most < 1 hr	Average 3.6 - 6.3 hr [24, 25, 50, 51]
Intervention duration	12 hr -14 days	3 days [24], 4 days [51] or 5 days [25, 50]
Outcome measures	Edema, lesion size, functional, cytokines	GOS-E, DRS, mortality at 1, 3, 6 months
Efficacy compared to placebo	Effective in majority of animal TBI trials [49, 183, 184]; Worse in female adolescence mice after CCI-TBI [185]; No effect on edema and lesion in rats after CCI-TBI [186]	Favorable outcome in moderate TBI but not in severe TBI in a Phase II study [24]; Favorable outcome in severe TBI in a Phase II study [25]; No benefits in the Phase III studies [50, 51]

Note: CCI=Controlled Cortical Impact, FPI=Fluid Percussion Injury; GCS = Glasgow Coma Scale, for classifying TBI severity; GOS = Glasgow Outcome Scale, as a common primary outcome measure in TBI; GOS-E=GOS-Extended (more sensitive than the GOS); DRS=Disability Rating Scale, for tracking the patient’s progress over time.