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

NCT00908063 | Terminated Phase 2 DMC

• 1 other identifier: OX-CL-II-005
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 6

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.

Conditions

Traumatic Brain Injury

Keywords

TBI; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• 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.

  Through Day 30 or hospital discharge

Secondary Outcomes (1)

• Efficacy as determined by short-term improvement

  Through Day 7, 30, Month 3, and Month 6

Study Arms (2)

Oxycyte

EXPERIMENTAL

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.

Drug: Oxycyte

Normal Saline

PLACEBO COMPARATOR

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.

Drug: Normal Saline

Interventions

Oxycyte DRUG

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).

Also known as: Oxycyte Perfluoro(t-butylcyclohexane) Intravenous Emulsion 60% w/v

Oxycyte

Normal Saline DRUG

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.

Also known as: Placebo

Normal Saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Severe chronic obstructive pulmonary disease (COPD), pulmonary edema, or congestive heart failure in the judgment of the Investigator
• Laboratory Values:
• Platelet count \<100,000/mm3 at screening, prior to transfusion of any platelets
• Neutrophil count \<1500 /mm3 at screening
• In the judgment of the Investigator, any clinically significant prolonged clotting time on INR, prothrombin time (PT) or activated partial thromboplastin time (aPTT), or any other coagulation test performed

Sponsors & Collaborators

• Tenax Therapeutics, Inc.: lead

Study Sites (6)

Soroka Medical Center

Beersheba, Ben Gurion, 84101, Israel

Location

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Sheba Medical Center

Ramat Gan, 52662, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Ospedale Regionale Lugano

Lugano, CH-TI, Switzerland

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

perfluoro(t-butylcyclohexane); Saline Solution

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Michael Reinert, MD

  Neurosurgery, Ospedale Regionale Lugano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2009
• First Posted: May 25, 2009
• Study Start: October 1, 2009
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: November 13, 2014

Record last verified: 2014-03

Locations

IL (5); CH (1)