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

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

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.

Study Overview

• Status: Completed
• Conditions: Blood Loss, Surgical
• Intervention / Treatment: Biological: rThrombin, 1000 IU/mL

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Arizona Burn Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: RECOTHROM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Days 1 through 29, continuously
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.	Days 1 through 29, continuously
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	Baseline and Day 29 from Baseline
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.	Baseline and Day 29 from Baseline
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.	Baseline and Day 29 from Baseline
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.	Baseline and Day 29 from Baseline
Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher	Grade 0=normal.	Baseline and Day 29 from Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Day 29

Collaborators and Investigators

• Sponsor: ZymoGenetics
• Investigators: Principal Investigator: Kevin Foster, MD, Arizona Burn Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 10, 2009
• First Posted (Estimate): March 11, 2009

Study Record Updates

• Last Update Posted (Estimate): January 26, 2012
• Last Update Submitted That Met QC Criteria: January 25, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Intraoperative Complications; Blood Loss, Surgical
• Other Study ID Numbers: 499H01