Clinical trial NCT00859547: Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants
Official title: A Phase 4, Open-Label, Single-Group Safety and Immunogenicity Study of RECOTHROM® (rThrombin) in Pediatric Subjects Undergoing Synchronous Burn Wound Excision and Skin Grafting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Blood Loss, Surgical
Lead sponsor: ZymoGenetics
Sponsor class: INDUSTRY
First posted: 2009-03-11
Enrollment: 30
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the safety and immunogenicity of recombinant thrombin (rThrombin) administered as an aid to hemostasis during burn wound excision and skin grafting in pediatric patients, newborn through 17 years of age.

Detailed description: The safety, immunogenicity, and efficacy of rThrombin have been evaluated in 5 Phase 2 studies, 1 pivotal Phase 3 study, and 1 Phase 3b study, in surgical indications such as: spinal surgery, major hepatic resection, peripheral arterial bypass surgery, arteriovenous graft formation for hemodialysis access, and burn wound excision. Limited data currently exist on the effects of rThrombin exposure in pediatric patients. This Phase 4 trial aims to provide additional information on the use of rThrombin in children by evaluating the drug's safety and immunogenicity when administered as an aid to hemostasis during burn wound excision and skin grafting in pediatric burn patients.

Eligibility criteria: Inclusion Criteria:

* Age of newborn through 17 years at time of enrollment
* At least 1 skin graft recipient site measuring at least 1% of total body surface area (TBSA)
* Total initial burn wounds estimated to measure less than 40% of TBSA
* Bleeding indicating treatment with rThrombin during the surgical procedure
* Females of child-bearing potential must have a negative urine or serum pregnancy test within 2 days prior to study-drug treatment
* informed consent document signed by legal representative (guardian) and approved by an institutional review board/independent ethics committee (IRB/IEC)
* Participant has signed an IRB/IEC-approved pediatric assent document, if applicable

Exclusion Criteria:

* Gestational age younger than 36 weeks at birth (for infants younger than 2 years)
* Documented active infection at the graft recipient site (participants with resolved infections at potential graft recipient sites are not excluded)
* Acute inhalation injury, as defined by bronchoscopic evidence of lower airway injury
* Currently undergoing autologous skin grafting for ischemic ulcer disease or cutaneous malignancies
* Presence of antibodies or hypersensitivity to the study drug or any of its components, other thrombin preparations, or coagulation factors
* Transfusion of whole blood, fresh frozen plasma, cryoprecipitate, or platelets within 24 hours prior to study-drug treatment (packed red blood cell transfusions are allowed)
* History of HIV infection or other immunodeficiency syndrome or is taking immunosuppressive or antirejection medications
* Medical, social, or psychosocial factors that, in the opinion of the investigator, could affect safety or compliance with study procedures
* Breastfeeding or being breastfed
* Treatment with any experimental agent within 30 days of study enrollment or treatment

Primary outcomes:
measure: Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity
timeFrame: Days 1 through 29, continuously
measure: Number of Participants With AEs by Maximum Severity
timeFrame: Days 1 through 29, continuously
measure: Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts
timeFrame: Baseline and Day 29 from Baseline
measure: Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels
timeFrame: Baseline and Day 29 from Baseline
measure: Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels
timeFrame: Baseline and Day 29 from Baseline
measure: Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher
timeFrame: Baseline and Day 29 from Baseline
measure: Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher
timeFrame: Baseline and Day 29 from Baseline
Secondary outcomes:
measure: Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody
timeFrame: At Day 29
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Burn Center
state: Arizona
Study officials:
affiliation: Arizona Burn Center
name: Kevin Foster, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Foster KN, Mullins RF, Greenhalgh DG, Gamelli RL, Glat P, Lentz CW, Kahn SA, Brandigi C, Fredlund P, Alexander WA. Recombinant human thrombin: safety and immunogenicity in pediatric burn wound excision. J Pediatr Surg. 2011 Oct;46(10):1992-9. doi: 10.1016/j.jpedsurg.2011.05.022.