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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00859547

Enrollment

Registered

2009-03-11

Start date

2009-03-31

Completion date

2010-01-31

Last updated

2012-01-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Blood Loss, Surgical

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.

Interventions

BIOLOGICALrThrombin, 1000 IU/mL

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

No minimum to 17 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher	Baseline and Day 29 from Baseline	Grade 0=normal.
Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity	Days 1 through 29, continuously	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	Days 1 through 29, continuously	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	Baseline and Day 29 from Baseline	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	Baseline and Day 29 from Baseline	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	Baseline and Day 29 from Baseline	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	Baseline and Day 29 from Baseline	ULN=upper limit of normal. Grade 0=normal; Grade 1=ULN to 1.5 x ULN.

Secondary

Measure	Time frame	Description
Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody	At Day 29	Antibody-positive was defined as seroconversion or ≥1.0 unit (≥10-fold) increase in titer compared with antibody titer at baseline.

Countries

United States

Participant flow

Recruitment details

Of the 32 participants who signed informed consent in this study, 30 were actually enrolled and received treatment with rThrombin.

Participants by arm

Arm	Count
rThrombin, 1000 IU/mL Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1.	30
Total	30

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1
Overall Study	Parent withdrew consent	1

Baseline characteristics

Characteristic	rThrombin, 1000 IU/mL
Age, Customized 0-2 years	11 participants
Age, Customized 12-17 years	8 participants
Age, Customized 3-6 years	8 participants
Age, Customized 7-11 years	3 participants
Race/Ethnicity, Customized American Indian/Alaskan native	1 participants
Race/Ethnicity, Customized Black or African American	6 participants
Race/Ethnicity, Customized Hispanic	9 participants
Race/Ethnicity, Customized White	14 participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	18 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	28 / 30
serious Total, serious adverse events	1 / 30

Outcome results

Primary

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.

Time frame: Days 1 through 29, continuously