Traumatic Brain InjuryPhase 2STOP-TBINCT00908063
Safety and Tolerability of Oxycyte in Patients With Traumatic Brain Injury (TBI)
A Phase 2 study testing Oxycyte and Normal Saline in people with Traumatic Brain Injury, run by Tenax Therapeutics, Inc. at 6 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Oxycyte and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Oct 2009to Sep 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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
- One or more of the following liver function test results: Total Bilirubin >2 x upper limit of normal (ULN), ALT >2.5 x ULN, or AST 2.5 > x ULN
- Women with a positive pregnancy test or known to be currently breastfeeding at screening
- Concomitant Medications:
- Known use of immunosuppressive therapy (e.g. TNF inhibitors, methotrexate, cyclosporine, etc.)
- Concurrent use of Plavix® (clopidogrel bisulfate), Pradaxa® (dabigatran elexilate) or an anti- coagulant other than ≤100 mg/day aspirin for any condition
- Known Medical History:
- Immersion injury
- Cardiopulmonary resuscitation (chest compression and/or external cardiac shock) required following the current injury
- Hemodynamically unstable (e.g., requiring >6L colloid or crystalloid fluid as well as >4 units of packed cells within 4 hours prior to enrollment)
- Known or suspected brain tumor
- Known severe allergy to any component of Oxycyte or known severe allergy to eggs
- Known to be immunocompromised (e.g. known history of HIV)
- Known history of major liver disease (e.g., liver failure, necrosis or cirrhosis) or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Any known hematological or coagulopathic disorder that, in the Investigator's opinion, is likely to significantly impair platelet function or coagulation (e.g., hemophilia, von Willebrand's disease, myelodysplastic syndrome)
- History of severe TBI (previous to the current TBI) or any prior cerebral injury that required hospitalization and that may, in the Investigator's opinion, interfere with the results of this study
- Known history of any of the following diseases: Parkinson's disease, Huntington's disease, major stroke, seizure disorder, multiple sclerosis or cerebral aneurysm (unless clipped and stable, in which case patient may be included)
- Any life threatening condition prior to the current injury or other diseases or disorders that, in the Investigator's opinion, may put the patient at undue risk or confound the results of the study (e.g signs of soft tissue or other active infection)
- Current participation in another clinical trial with an investigational product, or participation in such a clinical trial within 30 days prior to screening
- Patients serving in the military forces at the time of screening who (if required) do not have the necessary approval from the appropriate authorities
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Israel5 sites
Soroka Medical Center
Beersheba, Ben Gurion, 84101
Rambam Health Care Campus
Haifa, 31096
Hadassah Medical Center
Jerusalem, 91120
Sheba Medical Center
Ramat Gan, 52662
Tel-Aviv Sourasky Medical Center
Tel Aviv, 64239
About this study
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
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.
Read more
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.
Read the 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
- Being tested
- Oxycyte, Normal Saline
- Keywords
- TBI, Traumatic Brain Injury
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxycyteDrug
Also called Oxycyte Perfluoro(t-butylcyclohexane) Intravenous Emulsion 60% w/v
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).
Normal SalineDrug
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through Day 30 or hospital discharge
Secondary outcomes (1)
Efficacy as determined by short-term improvement
Short-term improvement will be compared between treatment groups as assessed by:
- Functional outcomes as measured by the Glasgow Outcome Scale-Extended (GOSE)
- Time to extubation
- Time to intensive care unit (ICU) discharge and
- Time to hospital discharge
Measured: Through Day 7, 30, Month 3, and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2009 (estimated)
- Study startOct 2009
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tenax Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Reinert, MD, Principal investigator, Neurosurgery, Ospedale Regionale Lugano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00908063
- Sponsor's protocol ID
- OX-CL-II-005
- Acronym
- STOP-TBI
- Status last verified
- Mar 2014
- First submitted
- 22 May 2009
- Last updated
- 13 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00908063
- Acronym / sponsor ID
- STOP-TBI / OX-CL-II-005
- Conditions
- Traumatic Brain Injury
- Keywords
- TBI, Traumatic Brain Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: futility
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Tenax Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 25 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxycyte | Experimental | Drug: OxycyteSingle 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. |
| Normal Saline | Placebo comparator | Drug: Normal SalineSingle 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxycyteAlso: Oxycyte Perfluoro(t-butylcyclohexane) Intravenous Emulsion 60% w/vA 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 | Oxycyte |
| Normal SalineAlso: PlaceboNormal 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. | Drug | Normal Saline |
Primary outcome
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
1 secondary outcome
Efficacy as determined by short-term improvement
Time frame: Through Day 7, 30, Month 3, and Month 6
Results and safety
The study was stopped early (reason given: futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Reinert, MD principal investigator
Neurosurgery, Ospedale Regionale Lugano
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxycyte and Normal Saline in people with Traumatic Brain Injury, run by Tenax Therapeutics, Inc. at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Israel, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2014.