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

Phase 3

Completed

• Conditions: Brain Injuries
• Interventions: Drug: Progesterone; Drug: Lipid emulsion without progesterone

• Registration Number: NCT01143064
• Lead Sponsor: BHR Pharma, LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-06-10
• Study First Submitted QC: 2010-06-10
• Study First Posted: 2010-06-14
• Primary Completion: 2014-03
• Study Completion: 2014-03
• Disposition First Submitted: 2014-06-11
• Disposition First Submitted QC: 2014-06-11
• Disposition First Posted: 2014-06-19
• Results First Submitted: 2022-05-23
• Status Verified: 2024-09
• Results First Submitted QC: 2024-09-05
• Last Update Submitted: 2024-09-05
• Results First Posted: 2024-10-02
• Last Update Posted: 2024-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1195

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Progesterone	Progesterone	-
Lipid emulsion without progestrone	Lipid emulsion without progesterone	-

Primary Outcome Measures

Name	Time	Method
Glasgow Outcome Scale (GOS)	6 months	The GOS 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

Name	Time	Method
Mortality at Month 1	1 month post injury	The mortality rate at one month will be compared between the two treatment groups.
Mortality at Month 6	6 months post injury	The mortality rate at six months will be compared between the two treatment groups.
Glasgow Outcome Scale at 3 Months	Month 3	The GOS assesses the mortality and disability in traumatic brain injury patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State, or Dead.
Glasgow Outcome Scale - Extended (GOS-E)	3 months and 6 months post injury	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)	3 months and 6 months post injury	The Short Form (36) Health Survey (SF-36) is a validated survey of patient health consisting of eight scaled scores which are the weighted sums of the questions in their section. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, role physical, role emotional, role mental and mental health. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)	Admission through post-infusion Day 6	Cerebral Perfusion Pressure (CPP) levels are presented according to clinically significant cut-off values. CPP was calculated from intracranial pressures and mean arterial pressures measured from Day through Day 6 after initiation of study medication, if an ICP monitor was in place. Specific therapies received during Days 1-6 are summarized according to the Therapeutic Intensity Level (TIL) by treatment group, as maximum level of therapy administered to the subject.

Trial Locations

Locations (156)

University of South Alabama Medical Center; 🇺🇸 Mobile, Alabama, United States

LAC+USC Medical Center; 🇺🇸 Los Angeles, California, United States

University of California San Diego Medical Center; 🇺🇸 San Diego, California, United States

Denver Health Medical Center; 🇺🇸 Denver, Colorado, United States

Christiana Care Health System Hospital; 🇺🇸 Newark, Delaware, United States

Delray Medical Center; 🇺🇸 Delray Beach, Florida, United States

Tallahassee Memorial Healthcare; 🇺🇸 Tallahassee, Florida, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

Saint Alphonsus Regional Medical Center; 🇺🇸 Boise, Idaho, United States

John H. Stroger Jr. Hospital of Cook County; 🇺🇸 Chicago, Illinois, United States

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