Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants
Primary Purpose
Blood Loss, Surgical
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
rThrombin, 1000 IU/mL
Sponsored by
About this trial
This is an interventional treatment trial for Blood Loss, Surgical
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
Sites / Locations
- Arizona Burn Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Recombinant thrombin (rThrombin), 1000 IU/mL
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment
Number of Participants With AEs by Maximum Severity
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. Mild=asymptomatic or minor symptoms; intervention not indicated. Moderate=requiring only minimal, local, or noninvasive intervention. Severe=significant symptoms but not life-threatening; hospitalization or invasive intervention indicated. Life-threatening=indicating intensive care or urgent invasive intervention.
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts
Abnormal laboratory findings were recorded as AEs when considered clinically significant (unusual for the surgical population or individual participant) by the investigator, when associated with symptoms, when requiring specific treatment, or when requiring a change in participant management.LLN=lower level of normal. Platelets: Grade 0=normal. WBC: Grade 0=normal. Lymphocytes: Grade 0=normal; Grade 1=<LLN x 0.8-10^9/L. Neutrophils: Grade 0=normal; Grade 1=<LLN-1.5x10^9/L; Grade 2=<1.5-1.0x10^9/L
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels
LLN=lower level of normal. Grade 1=100 g/L to <LLN; Grade 2=80 to <100 g/L; Grade 3=65 to <80 g/L; Grade 4=<65 g/L.
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels
ULN=upper level of normal. Grade 0=normal; Grade 1=>ULN to 1.5 x ULN.
Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher
ULN=upper limit of normal. Grade 0=normal; Grade 1=ULN to 1.5 x ULN.
Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher
Grade 0=normal.
Secondary Outcome Measures
Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody
Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00859547
Brief Title
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
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ZymoGenetics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Loss, Surgical
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Recombinant thrombin (rThrombin), 1000 IU/mL
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
rThrombin, 1000 IU/mL
Other Intervention Name(s)
RECOTHROM
Intervention Description
rThrombin,1000 IU/mL, 1000 IU/mL, applied topically to the bleeding site during a single surgery procedure on Day 1.
Primary Outcome Measure Information:
Title
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity
Description
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment
Time Frame
Days 1 through 29, continuously
Title
Number of Participants With AEs by Maximum Severity
Description
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. Mild=asymptomatic or minor symptoms; intervention not indicated. Moderate=requiring only minimal, local, or noninvasive intervention. Severe=significant symptoms but not life-threatening; hospitalization or invasive intervention indicated. Life-threatening=indicating intensive care or urgent invasive intervention.
Time Frame
Days 1 through 29, continuously
Title
Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts
Description
Abnormal laboratory findings were recorded as AEs when considered clinically significant (unusual for the surgical population or individual participant) by the investigator, when associated with symptoms, when requiring specific treatment, or when requiring a change in participant management.LLN=lower level of normal. Platelets: Grade 0=normal. WBC: Grade 0=normal. Lymphocytes: Grade 0=normal; Grade 1=<LLN x 0.8-10^9/L. Neutrophils: Grade 0=normal; Grade 1=<LLN-1.5x10^9/L; Grade 2=<1.5-1.0x10^9/L
Time Frame
Baseline and Day 29 from Baseline
Title
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels
Description
LLN=lower level of normal. Grade 1=100 g/L to <LLN; Grade 2=80 to <100 g/L; Grade 3=65 to <80 g/L; Grade 4=<65 g/L.
Time Frame
Baseline and Day 29 from Baseline
Title
Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Creatinine Levels
Description
ULN=upper level of normal. Grade 0=normal; Grade 1=>ULN to 1.5 x ULN.
Time Frame
Baseline and Day 29 from Baseline
Title
Number of Participants With Elevations in the Coagulation Parameter of Activated Partial Thromboplastin Time (aPPT)of Grade 0 or Higher
Description
ULN=upper limit of normal. Grade 0=normal; Grade 1=ULN to 1.5 x ULN.
Time Frame
Baseline and Day 29 from Baseline
Title
Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher
Description
Grade 0=normal.
Time Frame
Baseline and Day 29 from Baseline
Secondary Outcome Measure Information:
Title
Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody
Description
Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline.
Time Frame
At Day 29
10. Eligibility
Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Foster, MD
Organizational Affiliation
Arizona Burn Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arizona Burn Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85008
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22008340
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.
Results Reference
derived
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Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants
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