Safety and Tolerability of Oxycyte in Patients With Traumatic Brain Injury (TBI) (STOP-TBI)
The primary objective of this study is to evaluate the safety and tolerability of a single administration of Oxycyte in patients with severe non-penetrating traumatic brain injury (TBI).
In the first dose level (Cohort 1), 11 patients were randomized 2:1 to receive either 1.0 mL/kg Oxycyte (0.6 g/kg; n=8) or NS (n=3). A total of 8 patients received Oxycyte. The Data Safety Monitoring Board (DSMB) reviewed the safety data for patients in Cohort 1 through Day 14, and approved escalation to the next dose.
In Cohort 2, 18 patients will be randomized 2:1 to receive either 2.0 mL/kg Oxycyte (1.2 g/kg; n=12) or NS (n=6). The DSMB will then review the safety data for all patients in Cohort 2 through Day 14 and either approve escalation to the highest dose or remain at the current dose. If remaining at the current dose level (Cohort 2) an additional 50 patients will be randomized 1:1 to Oxycyte (n=25) or NS (n=25) and treated.
If escalation occurs to Cohort 3, 18 patients would be randomized 2:1 to Oxycyte (n=12) or NS (n=6) to receive the 3.0 mL/kg dose. The DSMB would again review the safety data and decide whether to treat an additional 50 patients at this dose, which would be randomized 1:1 to receive Oxycyte (n=25) or NS (n=25), or to decrease the dose back to 2.0 mL/kg. If the dose is reduced, an additional 50 patients will be randomized to receive Oxycyte (n=25) or NS (n=25) and treated at the 2.0 mL/kg dose.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Placebo Controlled, Double-Blind, Single Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of Oxycyte in Patients With Severe Non-Penetrating Traumatic Brain Injury|
- Safety as measured by incidence and severity of AEs/SAEs, thrombocytopenia, nosocomial infection and incidence of rebleed [ Time Frame: Through Day 30 or hospital discharge ] [ Designated as safety issue: Yes ]
- Efficacy as determined by 1. brain tissue oxygen tension, 2. neurological outcome as measured by GCS, and 3. functional outcome as measured by GOS-E [ Time Frame: Through Day 7, at Day 30, and at Months 3 and 6, respectively ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
|Experimental: Oxycyte Perfluorocarbon Emulsion||
A single dose of one of three dosage levels (dose escalating design), given by intravenous infusion at the rate of 15 mL/min (total duration expected to be between 5 and 20 minutes).
|Placebo Comparator: Normal Saline||
Drug: Normal Saline
Normal saline given via intravenous infusion at the rate of 15 mL/min at the volume that would be equivalent to the volume of Oxycyte if the patient were assigned to the active treatment group.
Randomized, double-blind, controlled, single administration, dose-escalation (up to three dose levels of Oxycyte) administered in conjunction with 50% oxygen (or greater, if per standard of care for a particular patient based on his / her condition, up to a maximum of 80%) and standard of care.
At each dose level, patients receiving Oxycyte will be compared to a control group of patients who will receive Normal Saline (NS); all patients will receive 50% oxygen or greater, if per standard of care for a particular patient based on his / her condition, up to a maximum of 80%.
If the Principal Investigator deems it necessary the patient may be temporarily placed on 100% O2 for a maximum of 2 hours.
Ischemic brain damage is found in 80% of patients who die from severe head injury and studies have shown that early, transient cerebral hypoperfusion of unknown origin is present in about 40% of these patients. Recently, new techniques have permitted continuous monitoring of brain oxygen tension and in a recently published study, it has been shown that about one-third of severe head injured patients have reduced brain oxygen tension (<25 mm Hg Hg02) for the first 6 to 12 hours following severe head injury. In this group of patients with low brain oxygen, outcome is significantly worse.
Since increasing brain oxygen tension by both FiO2 increase and HBO have shown benefit both in the lab and in patients, it is theorized that perfluorocarbon-enhanced oxygen delivery may provide the same or greater benefit. PFCs are especially attractive in this setting for several reasons; first, because they transport oxygen without the need for erythrocytes and hemoglobin and can thus perfuse and oxygenate "peri-contusional" brain tissue in which it has been shown that capillaries are so narrowed as to impede RBC transport; secondly, PFCs actually increase oxygen transport and oxygen tension in the tissues, which cannot be achieved with normobaric hyperoxia alone.
|Contact: Timothy Bradshaw, Ph.D.||firstname.lastname@example.org|
|Contact: Cathy Grill, BSNemail@example.com|
|Soroka Medical Center||Active, not recruiting|
|Beer Sheva, Ben Gurion, Israel, 84101|
|Rambam Health Care Campus||Recruiting|
|Haifa, Israel, 31096|
|Contact: Leon Levi, MD 972 04 854 2320 firstname.lastname@example.org|
|Contact: Menashe Zaaroor, Prof 97248542640 email@example.com|
|Principal Investigator: Menashe Zaaroor, MD|
|Principal Investigator: Leon Levi, MD|
|Hadassah Medical Center||Active, not recruiting|
|Jerusalem, Israel, 91120|
|Sheba Medical Center||Active, not recruiting|
|Ramat Gan, Israel, 52662|
|Tel-Aviv Sourasky Medical Center||Active, not recruiting|
|Tel-Aviv, Israel, 64239|
|Ospedale Regionale Lugano||Not yet recruiting|
|Lugano, Switzerland, CH-TI|
|Contact: Michael Reinert, Prof., MD|
|Principal Investigator: Michael Reinert, Prof., MD|
|Principal Investigator:||Michael Reinert, MD||Neurosurgery, Ospedale Regionale Lugano|