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

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

rThrombin, 1000 IU/mL

About this trial

This is an interventional treatment trial for Blood Loss, Surgical

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept 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

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

NCT ID

NCT00859547

First Posted

March 9, 2009

Last Updated

January 25, 2012

Sponsor

ZymoGenetics

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