Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Recombinant thrombin (rThrombin), 1000 IU/mL | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| 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=\ | Baseline and Day 29 from Baseline |
| Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kevin Foster, MD | Arizona Burn Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Burn Center | Phoenix | Arizona | 85008 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38837237 | Derived | 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. | |
| 22008340 | 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. |
Not provided
Not provided
Not provided
Of the 32 participants who signed informed consent in this study, 30 were actually enrolled and received treatment with rThrombin.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | rThrombin, 1000 IU/mL | Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | rThrombin, 1000 IU/mL | Recombinant thrombin (rThrombin), 1000 IU/mL, applied topically during a single surgery procedure on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Participants who received treatment with rThrombin. | Posted | Number | Participants | Days 1 through 29, continuously |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TOTAL | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| TRANSPLANT REJECTION | Immune system disorders | MedDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Pribble, Vice President, Medical Affairs; Scot Maxon, Scientific Information | ZymoGenetics | (206) 428-2756; (206) 434-3365 | John.Pribble@bms.com; Scot.Maxon@bms.com |
Not provided
| ID | Term |
|---|---|
| D016063 | Blood Loss, Surgical |
| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007431 | Intraoperative Complications |
Not provided
Not provided
| ID | Term |
|---|---|
| C513462 | recombinant human thrombin |
| D013917 | Thrombin |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
LLN=lower level of normal. Grade 1=100 g/L to \ |
| 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 |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
|
|
| 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. | Participants who received treatment with rThrombin. | Posted | Number | Participants | Days 1 through 29, continuously |
|
|
|
| Secondary | 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. | Participants who received study drug and had both baseline and on-treatment anti-rThrombin product antibody assessments. | Posted | Number | Participants | At Day 29 |
|
|
|
| Primary | 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=\ | Participants who received treatment with rThrombin. | Posted | Number | Participants | Baseline and Day 29 from Baseline |
|
|
|
| Primary | 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 \ | Participants who received treatment with rThrombin. | Posted | Number | Participants | Baseline and Day 29 from Baseline |
|
|
|
| Primary | 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. | Participants who received treatment with rThrombin. | Posted | Number | Participants | Baseline and Day 29 from Baseline |
|
|
|
| Primary | 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. | Participants who received treatment with rThrombin. | Posted | Number | Participants | Baseline and Day 29 from Baseline |
|
|
|
| Primary | Number of Participants With a High International Normalized Ratio (INR) of Prothrombin Time of Grade 0 or Higher | Grade 0=normal. | Participants who received treatment with rThrombin. | Posted | Number | Participants | Baseline and Day 29 from Baseline |
|
|
|
| 30 |
| 28 |
| 30 |
| SKIN GRAFT INFECTION | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| TRANSPLANT REJECTION | Immune system disorders | MedDRA 13.1 | Systematic Assessment |
|
| BACTERAEMIA | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| SKIN GRAFT INFECTION | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| PROCEDURAL PAIN | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| SEROMA | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| SKIN GRAFT FAILURE | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| WOUND SECRETION | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| EXCESSIVE GRANULATION TISSUE | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| HAEMATOMA | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
ZymoGenetics (ZG) agreements vary by trial, but each states that presentation/publication (p/p) cannot disclose Confidential Information (CI), excluding trial results; p/p may not begin until the earlier of 18 months after study end, ZG/lead investigator publishes, or ZG notification that multicenter publication is not planned; ZG has specified time for draft review before submission/presentation and may delay or modify content, require CI removal, and delay p/p for patent application filing.
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
| Title | Measurements |
|---|---|
|
| Mild (12-17 years, n=8) |
|
| Moderate (0-2 years, n=11) |
|
| Moderate (3-6 years, n=8) |
|
| Moderate (7-11 years, n=3) |
|
| Moderate (12-17 years, n=8) |
|
| Severe (0-2 years, n=11) |
|
| Severe (3-6 years, n=8) |
|
| Severe (7-11 years, n=3) |
|
| Severe (12-17 years, n=8) |
|
| Life-threatening (0-2 years, n=11) |
|
| Life-threatening (3-6 years, n=8) |
|
| Life-threatening (7-11 years, n=3) |
|
| Life-threatening (12-17 years, n=8) |
|
| Title | Measurements |
|---|---|
|
| Grade 0, low WBC (Day 29, N=26) |
|
| Grade 0, low lymphocytes (Baseline, N=29) |
|
| Grade 0, low lymphocytes (Day 29, N=25) |
|
| Grade 1, low lymphocytes (Baseline, N=29) |
|
| Grade 1, low lymphocytes (Day 29, N=25) |
|
| Grade 0, neutrophils (Baseline, N=29) |
|
| Grade 0, neutrophils (Day 29, N=25) |
|
| Grade 2, low neutrophils (Baseline) |
|
| Grade 2, low neutrophils (Day 29, N=25) |
|
| Title | Measurements |
|---|---|
|
| Grade 2 low hemoglobin (Day 29, N=26) |
|
| Grade 3 low hemoglobin (Baseline) |
|
| Grade 3 low hemoglobin (Day 29, N=26) |
|
| Grade 4 low hemoglobin (Baseline) |
|
| Grade 4 low hemoglobin (Day 29, N=26) |
|
| Title | Measurements |
|---|
|
| Grade 1 high creatinine (Day 29, N=26) |
|
| Title | Measurements |
|---|---|
|
| Grade 1 high aPPT (Day 29, N=24) |
|