Safety and Immunogenicity Study of Recombinant Thrombin (rThrombin) in Pediatric Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ZymoGenetics
ClinicalTrials.gov Identifier:
NCT00859547
First received: March 9, 2009
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Blood Loss, Surgical
Biological: rThrombin, 1000 IU/mL
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ZymoGenetics:

Primary Outcome Measures:
  • Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity [ Time Frame: Days 1 through 29, continuously ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Days 1 through 29, continuously ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Day 29 from Baseline ] [ Designated as safety issue: No ]
    Grade 0=normal.


Secondary Outcome Measures:
  • Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody [ Time Frame: At Day 29 ] [ Designated as safety issue: No ]
    Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline.


Enrollment: 30
Study Start Date: March 2009
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Recombinant thrombin (rThrombin), 1000 IU/mL Biological: rThrombin, 1000 IU/mL
rThrombin,1000 IU/mL, 1000 IU/mL, applied topically to the bleeding site during a single surgery procedure on Day 1.
Other Name: RECOTHROM

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

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00859547

Locations
United States, Arizona
Arizona Burn Center
Phoenix, Arizona, United States, 85008
Sponsors and Collaborators
ZymoGenetics
Investigators
Principal Investigator: Kevin Foster, MD Arizona Burn Center
  More Information

No publications provided by ZymoGenetics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ZymoGenetics
ClinicalTrials.gov Identifier: NCT00859547     History of Changes
Other Study ID Numbers: 499H01
Study First Received: March 9, 2009
Results First Received: November 3, 2011
Last Updated: January 25, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hemorrhage
Blood Loss, Surgical
Pathologic Processes
Intraoperative Complications
Thrombin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014