NCT00908063

Safety and Tolerability of Oxycyte in Patients With Traumatic Brain Injury (TBI)

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Tenax Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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 or to decrease the dose back to 2.0 mL/kg. This group would be randomized 1:1 to receive Oxycyte (n=25) or NS.

Detailed description

This is 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 administered in conjunction with 50% to 80% oxygen and standard of care treatment. 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%. 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. In several early research studies, it is documented that about one-third of severe head injured patients have reduced brain oxygen tension (\<25 mm Hg) especially during the first 6 to 12 hours following severe head injury. In this group of patients with low brain oxygen, the clinical prognosis is poor with death being a frequent outcome. Based on a belief that increased brain oxygen levels would prove beneficial in the TBI patient, 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 red blood cell (RBC) transport; secondly, perfluorocarbon (PFCs) actually increase oxygen transport and oxygen tension in the tissues, which cannot be achieved with normobaric hyperoxia alone.

Conditions

• Traumatic Brain Injury

Interventions

Type	Name	Description
DRUG	Oxycyte	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).
DRUG	Normal Saline	Normal saline will be administered as one of three volume doses based on cohort assignment (1.0 mL/min; 2.0 mL/min; 3.0 mL/min). The infusion will be administered at a rate of 15mL/min and will begin within 12 hours of injury.

Timeline

• Start date: 2009-10-01
• Primary completion: 2014-09-01
• Completion: 2014-09-01
• First posted: 2009-05-25
• Last updated: 2014-11-13

Locations

6 sites across 2 countries: Israel, Switzerland