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
Overview
- Phase
- Phase 2
- Intervention
- Oxycyte
- Conditions
- Traumatic Brain Injury
- Sponsor
- Tenax Therapeutics, Inc.
- Enrollment
- 18
- Locations
- 6
- Primary Endpoint
- Safety and tolerability will be compared between treatment groups as measured by frequency, severity, and type of adverse events and serious adverse events between treatment groups.
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female 18 - 70 years of age (inclusive) at the time of study entry
- •Weight ≥45 kg
- •Able to begin the infusion of study drug within 12 hours of injury
- •Evidence of severe non-penetrating traumatic brain injury by clinical evaluation, clinical indication for intracranial pressure (ICP) monitoring, Glasgow Coma Scale (GCS) assessment (4-8 prior to randomization, obtained any time prior to dosing and including patients who deteriorate to severe TBI after arrival in the hospital, not including times when the patient is pharmacologically paralyzed for management or treatment) and with definite anatomic signs of injury on head CT scan (e.g., Marshall Grade II-VI or equivalent)
- •At least one reactive pupil at screening. Just prior to study drug administration pupil reactivity must be confirmed again. If the patient is in the peri-postoperative period at that time and reactivity is difficult to assess due to small pupil size, the Investigator will determine if the patient is eligible based on clinical presentation.
- •If a patient, due to his or her injuries is unable to provide written informed consent, then written consent may be obtained by an appropriate surrogate decision maker in accordance with preapproved procedures in compliance with local regulations.
Exclusion Criteria
- •Patients who meet any of the following criteria will not be included in the study:
- •Physical Assessment:
- •Not expected to survive the next 24 hours
- •Morbidly obese (BMI \>40)
- •Absence of a motor response (not including times when the patient is pharmacologically paralyzed for management or treatment)
- •Severe unexpected hyperthermia on admission (e.g. \>39°C)
- •Bilaterally fixed and dilated pupils
- •Penetrating traumatic brain injury
- •Major liver, kidney, or cardiac injury requiring operative intervention
- •Major pulmonary injury, including lung contusion, severe atelectasis, acute respiratory distress syndrome, or acute aspiration pneumonitis
Arms & Interventions
Oxycyte
Single intravenous infusion of Oxycyte (Perfluoro(t-butylcyclohexane) Intravenous Emulsion 60% w/v) 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.
Intervention: Oxycyte
Normal Saline
Single intravenous infusion of Normal Saline 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.
Intervention: Normal Saline
Outcomes
Primary Outcomes
Safety and tolerability will be compared between treatment groups as measured by frequency, severity, and type of adverse events and serious adverse events between treatment groups.
Time Frame: Through Day 30 or hospital discharge
Secondary Outcomes
- Efficacy as determined by short-term improvement(Through Day 7, 30, Month 3, and Month 6)