CTRI/2013/02/003396.

Trial name or title	A randomised, placebo‐controlled study to investigate the efficacy of progesterone in patients with severe traumatic brain injury
Methods	RCT
Participants	Inclusion criteria: men and women aged 16‐70 years (inclusive); weighing 45 kg‐135 kg (inclusive); who had sustained a closed head trauma ≤ 8 h before initiation of study drug infusion; TBI diagnosed by history and clinical examination; post‐resuscitation GCS score 4‐8 (inclusive); at least 1 reactive pupil; evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (diffuse injury II‐IV, evacuated and non‐evacuated mass lesion, Marshall's CT Classification) Exclusion criteria: life expectancy < 24 hours as determined by the Investigator; prolonged and/or uncorrectable hypoxia or hypotension (systolic blood pressure 90 mmHg) upon admission; any spinal cord injury; pregnant; penetrating head injury; bilaterally fixed dilated pupils at the time of randomisation; coma suspected to be primarily due to other causes (e.g. alcohol); pure epidural haematoma; pre‐existing clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome; severe cardiac or haemodynamic instability after resuscitation; known treatment with other investigational drug therapy or procedure within 30 days of injury; a history of allergic reaction to progesterone and related drugs or any of the components of the infusion; any disease that, in the opinion of the investigator, is unstable or which could jeopardise the safety of the patient and his/her compliance in the study; those who, in the opinion of the investigator, would not be able or willing to comply with the protocol through the final visit (6 months postinjury)
Interventions	Intervention group: progesterone 1.0 mg/kg via intramuscular injection, repeated every 12 hours for 5 consecutive days Control group: distilled water 1.0 mg/kg via intramuscular injection, repeated every 12 hours for 5 consecutive days
Outcomes	Primary outcome: GOS at 6 months postinjury Secondary outcomes: mortality at 1 and 6 months postinjury; GOS at 3 months postinjury; GOS‐E at 3 and 6 months; quality of life using SF‐36 at 3 and 6 months; change in ICP and cerebral perfusion pressure; changes in intracranial pathology as assessed by admission and day 6 CT scans; changes in biochemical markers of severe TBI at 120 hours after the administration of the drug/ placebo
Starting date	July 2013
Contact information	Dr Sumit Sinha, sumitaiims@yahoo.com Department of Neurosurgery, JPNA Trauma Center, All India Institute of Medical Sciences‐110029 New Delhi, DELHI
Sponsors and Collaborators	All India Institute of Medical Sciences
Notes	Estimated enrollment: 80 participants