Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury (SyNAPSe)

This study has been completed.
Sponsor:
Collaborators:
PRA International
INC Research
Information provided by (Responsible Party):
BHR Pharma, LLC
ClinicalTrials.gov Identifier:
NCT01143064
First received: June 10, 2010
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

The SyNAPSe trial will study if giving intravenous (i.v.) progesterone within 8 hours of the injury for a total of 120 hours to severe traumatic brain injury patients improves their recovery.


Condition Intervention Phase
Brain Injuries
Drug: Progesterone
Drug: Lipid emulsion without progesterone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Investigate the Efficacy and Safety of Progesterone in Patients With Severe Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by BHR Pharma, LLC:

Primary Outcome Measures:
  • Glasgow Outcome Scale (GOS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The GOS (Jennett and Bond, 1975) assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead.


Secondary Outcome Measures:
  • Mortality [ Time Frame: 1 month and 6 months post injury ] [ Designated as safety issue: Yes ]
    The mortality rate at one and six months will be compared between the two treatment groups.

  • Glasgow Outcome Scale [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  • Glasgow Outcome Scale - Extended (GOS-E) [ Time Frame: 3 months and 6 months post injury ] [ Designated as safety issue: No ]

    The GOS-E assessment of mortality and disability in TBI patients extends the original five GOS categories of functional outcome to eight categories:

    • Dead
    • Vegetative State
    • Lower Severe Disability
    • Upper Severe Disability
    • Lower Moderate Disability
    • Upper Moderate Disability
    • Lower Good Recovery
    • Upper Good Recovery

  • Short Form (36) Health Survey (SF-36) [ Time Frame: 3 months and 6 months post injury ] [ Designated as safety issue: No ]

    The SF-36 is a validated survey of patient health consisting of eight scaled scores. The eight sections are:

    • vitality
    • physical functioning
    • bodily pain
    • general health perceptions
    • role physical
    • role emotional
    • role mental
    • mental health

    The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health.


  • Effect of progesterone on Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), and Therapeutic Intensity Level (TIL) [ Time Frame: Admission through post-infusion Day 6 ] [ Designated as safety issue: No ]
  • Effect of progesterone on the progression of intracranial pathology [ Time Frame: Admission and Day 6 computed tomography (CT) scans ] [ Designated as safety issue: No ]

Enrollment: 1195
Study Start Date: June 2010
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Progesterone Drug: Progesterone
Intravenous administration of 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.
Other Name: BHR-100
Placebo Comparator: Lipid emulsion without progestrone Drug: Lipid emulsion without progesterone
Intravenous administration equal to 0.71mg/kg/hr for 1hr followed by 0.5mg/kg/hr administered intravenously for an additional 119 hrs.

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients between the age of 16 and 70 years, inclusive
  2. Weight from 45 to 135 kg, inclusive
  3. Sustained a closed head trauma no more than 8 hours before start of study drug infusion
  4. TBI diagnosed by history and clinical examination
  5. Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive
  6. At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive)
  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

Exclusion Criteria:

  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) at the time of randomization
  3. Any spinal cord injury
  4. Pregnancy
  5. 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 prior to randomization
  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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01143064

  Show 156 Study Locations
Sponsors and Collaborators
BHR Pharma, LLC
PRA International
INC Research
Investigators
Study Director: Neta R. Nelson, MPH BHR Pharma, LLC
  More Information

Additional Information:
Publications:
Responsible Party: BHR Pharma, LLC
ClinicalTrials.gov Identifier: NCT01143064     History of Changes
Other Study ID Numbers: BHR-100-301, 2010-018283-16
Study First Received: June 10, 2010
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Malaysia: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan: Center for Drug Evaluation
Thailand: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by BHR Pharma, LLC:
Brain Injury
Trauma

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014