The aim of the study is to determine the efficacy and safety of BHR-100 i.v. progesterone infusion compared to placebo infusion, utilizing the GOS in severe traumatic brain injury patients (GCS 3-8), with the treatment administered continuously over…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
traumatisch hersenletsel
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
GOS evaluated at 6 months post injury.
Secondary outcome
* Mortality assessment at 1 month and 6 months post TBI
* Evaluation of GOS at 3 months
* Evaluation of the GOS-E at 3 and 6 months
* Quality of Life (SF-36) at 3 and 6 months
* Impact of treatment on ICP, CPP, and TIL
* Effect of treatment on the progression of intracranial pathology as assessed
by admission (baseline) and day 6 (+/-1 Day) end-infusion CT scans
Background summary
Studies have shown that administering relatively large doses of progesterone
during the first few hours to days after injury significantly limits central
nervous system damage, reduces loss of neural tissue, and improves functional
recovery. Although the research published to date has focused primarily on
progesterone's effects on blunt TBI, there is evidence that the hormone affords
protection from several forms of acute central nervous system injury, including
penetrating brain trauma, stroke, anoxic brain injury, and spinal cord injury.
Progesterone appears to exert its protective effects by protecting or restoring
the blood-brain barrier, attenuating cerebral edema, down-regulating the
inflammatory cascade, and limiting cellular necrosis and apoptosis. All are
plausible mechanisms of neuroprotection (Stein, 2008).
Study objective
The aim of the study is to determine the efficacy and safety of BHR-100 i.v.
progesterone infusion compared to placebo infusion, utilizing the GOS in severe
traumatic brain injury patients (GCS 3-8), with the treatment administered
continuously over 5 days beginning within 8 hours after the injury. In
addition, the safety and clinical benefit of BHR-100 treatment will be assessed
through the secondary endpoints.
Study design
This trial will be a multicenter, randomized, double-blind, placebo-controlled
study, conducted in approximately 140 Level I (or equivalent) trauma centers in
various geographical areas including North America, Europe, Asia, and South
America.
The subjects will be managed in accordance with the standard guidelines for the
management of severe TBI: BTF, ABIC, and EBIC (BTF, 2007; ABIC, 2003; Maas et
al., 1997, respectively).
An independent DSMB will be appointed to have responsibility for safeguarding
the interests of trial subjects, and assessing the safety and efficacy of the
study treatments during the trial.
Treatment allocation will be done using a centralized randomization system.
Intervention
A loading dose of 0.71 mg/kg/hr of BHR-100 or placebo i.v. for the first hour
will be followed by a continuous maintenance infusion of 0.5 mg/kg/hr for a
total of 5 days/120 hours of treatment. The study drug treatment (BHR-100 or
placebo) is administered by i.v. infusion via peristaltic pump and must be
started within 8 hours after injury.
A total of 5 days (120 hours) of continuous infusion treatment.
Study burden and risks
Progesterone for the treatment of traumatic brain injury has been tested in
three human studies.
In these trials, the only side effect attributed to progesterone was
inflammation of the vein at the site of infusion in one patient, and this did
not require medical treatment.
These three studies used various mixtures of progesterone. The mixture of
progesterone in BHR-100 has not yet been studied in patients with severe
traumatic brain injury.
The following potential risks were previously identified as associated with
prolonged (greater than 3 months) administration of progesterone (in women):
Common Side Effects (> 5% of subjects):
* Chest pain
* Viral infection
* Migraine (severe headache)
Rare Side Effects (< 1% of subjects):
* Heart attack
* Blood clots
* Stroke
* Liver function abnormalities
* Pneumonia
* Meningitis
* Allergic reaction
* Abnormal vision
* Fluid retention
There may be other side effects that are not known at this time.
Blood Collection
There may be pain, swelling, or bruising around the vein where your blood was
collected. Subject may get an infection at the place on your body from which
the blood was collected.
Risks to Unborn Children
Women who are pregnant or nursing a child may not take part in this study.
There may be risks to the embryo or fetus should you become pregnant which are
currently unknown.
Herndon Parkway, Suite 110 607
Herndon VA 20170
US
Herndon Parkway, Suite 110 607
Herndon VA 20170
US
Listed location countries
Age
Inclusion criteria
1. Male or female patients, age between 18 and 70 years, inclusive (or 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 (exposed dura mater is acceptable in the case of depressed skull fractures)
4. TBI diagnosed by history and clinical examination
5. GCS score between 3 and 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, device, medical
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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-018283-16-NL |
| ClinicalTrials.gov | NCT01143064 |
| CCMO | NL32418.029.10 |