Study Design

The SyNAPSe study is a multicenter, randomized, double-blind, placebo-controlled clinical trial, conducted in at least 100 Level I (or equivalent) trauma centers worldwide.

Patients must be managed in accordance with the Brain Trauma Foundation (BTF), ABIC or EBIC guidelines for the care of severe TBI. Patients are administered either BHR-100 or placebo infusion by peristaltic infusion pump for a duration of 5 days (120 hours). A loading dose of BHR-100 or placebo for the first hour is followed by a continuous maintenance infusion for a total of 120 hours of treatment. The study treatment must begin within 8 hours after injury.

Prospective study patients need to meet the following criteria:

  1. Male or female patients, age between 16 and 70 years, inclusive (or the lower age limit as required by local regulations)
  2. Weight from 45 to 135 kg, inclusive
  3. Sustained a closed head trauma no more than 8 hours before initiation of study drug infusion
  4. TBI diagnosed by history and clinical examination
  5. Post-resuscitation GCS score between 4 to 8, inclusive
  6. At least one reactive pupil
  7. 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)
  8. Indication for ICP monitoring

Patients are excluded from the study for the following conditions:

  1. Life expectancy of less than 24 hours as determined by the Investigator
  2. Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood pressure < 90 mmHg) upon admission
  3. Any spinal cord injury
  4. Pregnancy
  5. Patients with penetrating head injury
  6. Bilaterally fixed dilated pupils at the time of randomization
  7. Coma suspected to be primarily due to other causes (e.g. alcohol)
  8. Pure epidural hematoma
  9. Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome
  10. Severe cardiac or hemodynamic instability after resuscitation
  11. Known treatment with another investigational drug therapy or procedure within 30 days of injury
  12. A history of allergic reaction to progesterone and related drugs or any of the components of the infusion
  13. Any disease, in the opinion of the Investigator, that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
  14. Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol through the final visit (6 months post-injury)

Investigational drugs or therapies, as well as the following specific interventions, should be avoided if at all possible when treating subjects enrolled in this study:

  • Hypothermia (less than or equal to 35°C)
  • Prophylactic hyperventilation (for-cause hyperventilation is allowed)
  • Prophylactic decompression craniectomy (decompression craniectomy is allowed for refractory ICP if more conservative measures have failed)
  • Hyperbaric oxygen therapy