Clinical trial NCT00301483: A Single Site Safety and Tolerability Study of HBOC-201 in Trauma Subjects
Official title: A Single-Center, Study to Evaluate the Safety and Tolerability of Hemoglobin-Based Oxygen Carrier-201 (HBOC 201) in Trauma Subjects. (Phase II - Safety and Tolerability)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Wounds and Injuries
Keywords: multiple trauma
bleeding injuries
gunshot wounds
stab wounds
penetrating injuries
blunt trauma
multiple wounds
Lead sponsor: Biopure Corporation
Sponsor class: INDUSTRY
First posted: 2006-03-13
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to determine if HBOC-201 is safe and tolerable to trauma subjects, when given to treat the inadequate supply of blood and nutrients to tissues and organs.

Detailed description: This Phase II study will be a single-center, randomized, single-blind, parallel-group, standard therapy-controlled, variable dose study of HBOC 201 administered to trauma subjects with bleeding or potential for bleeding who require standard fluid therapy for treatment of hypoperfusion. The type and incidence of adverse events and serious adverse events attributed to the study drug will be analyzed.

Secondary variables in this safety and tolerability study, will be summarized with descriptive statistics and frequency tables. The purpose of this data collection is to assess efficacy variables and the feasibility of utilizing these parameters in future trauma studies that will assess parameters of morbidity and mortality and include, but are not limited to:

* Time to improvement of serum (or plasma) lactate
* Time to improvement in the Base Deficit
* Time to maintained stability (BD\<5) over 24 hours
* Overall improvement in Base Deficit over 24 Hours
* Stability of subjects at 24 hours
* Time to meet treatment-stopping criteria
* Volume to meet treatment-stopping criteria
* Incidence of infectious complications (e.g., incidence of ventilator-associated pneumonia)
* Length of time on ventilator
* Incidence of multiple organ dysfunction (MOD)

Hemorrhage with subsequent hypoperfusion is a major cause of both immediate and delayed death in subjects who have sustained traumatic injuries. Effective therapies for hemorrhage to treat hypoperfusion that can be given immediately following injury are lacking. The following issues confound this problem further:

* Hemorrhaging trauma victims often have an immediate need for therapy to ensure adequate delivery of oxygen to vital tissues;
* Standard of care fluids such as Lactated Ringers Solution do not provide oxygen and blood can not be readily stored, transported or easily used in pre-hospital settings
* In the absence of oxygen-carrying fluid, traditional approaches to sustain vital organ perfusion, such as administration of intravenous fluid therapy, may have detrimental effects if given prior to hemostasis in certain subjects, particularly those with penetrating truncal injuries.

Eligibility criteria: INCLUSION CRITERIA:

* Male or Female (females not of childbearing potential or negative pregnancy test prior to enrollment)
* Age ≥ 18 years and ≤ 65 years of age
* Trauma with bleeding or a potential for bleeding arriving at initial treatment facility directly from scene of injury
* Subject should be enrolled within four (4) hours of injury
* Base Deficit (BD) greater than 5.0 and one of the following:

Systolic Blood Pressure ≤ 100 mm Hg OR Sustained (≥ 10 minutes) Heart Rate ≥ 100

* No localized signs of traumatic brain injury and a Glasgow Coma Score of ≥9 with the exception of drug-induced lowered GCS.
* Informed consent, or independent physician authorization obtained

EXCLUSION CRITERIA:

* Known or suspected Traumatic Brain Injury
* Non-survivable injury (Falcone Criteria)
* Traumatic arrest
* Known prior cardiac arrest (i.e., preceding trauma episode)
* Known or suspected pregnancy
* Known allergy to bovine products
* Prior treatment with blood (subsequent to current trauma)
* Informed consent or independent physician authorization unable to be obtained
* Unable to meet protocol or follow-up criteria

Primary outcomes:
measure: Safety/Tolerability of HBOC-201 for treatment of hypoperfusion in trauma by analysis of AEs/SAEs attributed to study drug
timeFrame: Duration of the study (Randomization through 28-day follow-up)
Secondary outcomes:
measure: Efficacy/feasibility of the following measurements in trauma studies (list is not all inclusive): Time to serum lactate improvement, Base deficit (BD) improvement, BD > 5 over 24 hrs, 24 hr stability, Infection, Vent time
timeFrame: Duration of the study (Randomization through 28-day follow-up)
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Department of Surgery: Johannesburg Hospital
state: Gauteng
Study officials:
affiliation: Biopure Corporation
name: A. Gerson Greenburg, MD, PhD
role: STUDY_DIRECTOR
affiliation: Wits University Medical School
name: Professor Ken D Boffard, MD
role: PRINCIPAL_INVESTIGATOR
References: