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

NCT00859547 | Completed Phase 4 Results DMC

• 1 other identifier: 499H01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Blood Loss, Surgical

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (1)

• Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody

  At Day 29

Study Arms (1)

Recombinant thrombin (rThrombin), 1000 IU/mL

EXPERIMENTAL

Biological: rThrombin, 1000 IU/mL

Interventions

rThrombin, 1000 IU/mL BIOLOGICAL

rThrombin,1000 IU/mL, 1000 IU/mL, applied topically to the bleeding site during a single surgery procedure on Day 1.

Also known as: RECOTHROM

Recombinant thrombin (rThrombin), 1000 IU/mL

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ZymoGenetics: lead

Study Sites (1)

Arizona Burn Center

Phoenix, Arizona, 85008, United States

Location

Related Publications (2)

• Sinha S, Gabriel VA, Arora RK, Shin W, Scott J, Bharadia SK, Verly M, Rahmani WM, Nickerson DA, Fraulin FO, Chatterjee P, Ahuja RB, Biernaskie JA. Interventions for postburn pruritus. Cochrane Database Syst Rev. 2024 Jun 5;6(6):CD013468. doi: 10.1002/14651858.CD013468.pub2.

  PMID: 38837237 DERIVED

• 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.

  PMID: 22008340 DERIVED

MeSH Terms

Conditions

Blood Loss, Surgical

Interventions

recombinant human thrombin; Thrombin

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Results Point of Contact

• Title: John Pribble, Vice President, Medical Affairs; Scot Maxon, Scientific Information
• Organization: ZymoGenetics

John.Pribble@bms.com; Scot.Maxon@bms.com

(206) 428-2756; (206) 434-3365

Study Officials

• Kevin Foster, MD

  Arizona Burn Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2009
• First Posted: March 11, 2009
• Study Start: March 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: January 26, 2012
• Results First Posted: December 8, 2011

Record last verified: 2012-01

Locations

US (1)