Blood Loss, SurgicalPhase 4NCT00859547

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

A Phase 4 study testing rThrombin, 1000 IU/mL in people with Blood Loss, Surgical, run by ZymoGenetics at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages Up to 17 years
Conditions the study is for: Blood Loss, Surgical
What is being tested?: rThrombin, 1000 IU/mL
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: Mar 2009to Jan 2010
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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)

Show all 10Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Arizona Burn Center
Phoenix, Arizona, 85008

Other trials in United States

About this study

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

Read the 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.

Conditions: Blood Loss, Surgical
Being tested: rThrombin, 1000 IU/mL
Medical subject headings: Blood Loss, Surgical

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT00859547
Study group	Role	What they receive
Recombinant thrombin (rThrombin), 1000 IU/mL	Experimental	Not described Receives: Biological: rThrombin, 1000 IU/mL

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and Day 29 from Baseline

Secondary outcomes (1)

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.
Measured: At Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2009Jan 2010

First posted11 Mar 2009 (estimated)
Study startMar 2009
Primary completionJan 2010
Study completionJan 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Blood Loss, SurgicalStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00859547
Sponsor's protocol ID: 499H01
Status last verified: Jan 2012
First submitted: 9 Mar 2009
Last updated: 26 Jan 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 38837237
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.
PubMed 22008340

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00859547
Acronym / sponsor ID: 499H01
Conditions: Blood Loss, Surgical
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: ZymoGeneticsIndustry (pharma, biotech, devices)
Study start: Mar 2009
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 11 Mar 2009 (estimated)
Results: Posted 8 Dec 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Recombinant thrombin (rThrombin), 1000 IU/mL	Experimental	Biological: rThrombin, 1000 IU/mL

Who may qualify

Ages: Up to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

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

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rThrombin, 1000 IU/mLAlso: RECOTHROMrThrombin,1000 IU/mL, 1000 IU/mL, applied topically to the bleeding site during a single surgery procedure on Day 1.	Biological	Recombinant thrombin (rThrombin), 1000 IU/mL

Primary outcome

Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and Day 29 from Baseline
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
Time frame: Baseline and Day 29 from Baseline
Grade 0=normal.

1 secondary outcome

Number of Participants WIth Positive Findings for Anti-rThrombin Product Antibody
Time frame: At Day 29

Results and safety

Results posted to the registry on 8 Dec 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
rThrombin, 1000 IU/mL	30	28

Primary outcome: Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity

Time frame: Days 1 through 29, continuously. Number. Unit: Participants

Measure	rThrombin, 1000 IU/mL n = 30
Deaths	0
Serious adverse events	1
Treatment-related adverse events (AEs)	0
AEs leading to discontinuation	0
AEs of hypersensitivity	3

Population analysed: Participants who received treatment with rThrombin.

Primary outcome: Number of Participants With AEs by Maximum Severity

Time frame: Days 1 through 29, continuously. Number. Unit: Participants

Measure	rThrombin, 1000 IU/mL n = 30
Mild (0-2 years, n=11)	3
Mild (3-6 years, n=8)	3
Mild (7-11 years, n=3)	0
Mild (12-17 years, n=8)	3
Moderate (0-2 years, n=11)	1
Moderate (3-6 years, n=8)	5
Moderate (7-11 years, n=3)	3
Moderate (12-17 years, n=8)	3

Population analysed: Participants who received treatment with rThrombin.

Primary outcome: Number of Participants With Clinical Laboratory Findings of Grade O or Higher in Platelet, White Blood Cell (WBC), Lymphocyte, and Neutrophil Counts

Time frame: Baseline and Day 29 from Baseline. Number. Unit: Participants

Measure	rThrombin, 1000 IU/mL n = 30
Grade 0, low platelets (Baseline)	30
Grade 0, low platelets (Day 29, N=25)	25
Grade 0, low WBC (Baseline)	30
Grade 0, low WBC (Day 29, N=26)	26
Grade 0, low lymphocytes (Baseline, N=29)	28
Grade 0, low lymphocytes (Day 29, N=25)	25
Grade 1, low lymphocytes (Baseline, N=29)	1
Grade 1, low lymphocytes (Day 29, N=25)	0

Population analysed: Participants who received treatment with rThrombin.

Primary outcome: Number of Participants With Clinical Laboratory Findings of Grade 0 or Higher in Hemoglobin Levels

Time frame: Baseline and Day 29 from Baseline. Number. Unit: Participants

Measure	rThrombin, 1000 IU/mL n = 30
Grade 1 low hemoglobin (Baseline)	13
Grade 1 low hemoglobin (Day 29, N=26)	7
Grade 2 low hemoglobin (Baseline)	4
Grade 2 low hemoglobin (Day 29, N=26)	5
Grade 3 low hemoglobin (Baseline)	1
Grade 3 low hemoglobin (Day 29, N=26)	0
Grade 4 low hemoglobin (Baseline)	0
Grade 4 low hemoglobin (Day 29, N=26)	0

Population analysed: Participants who received treatment with rThrombin.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TOTAL	1 of 30 (3.3%)	28 of 30 (93.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38837237Sinha 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.
Derived from this study: PubMed 22008340Foster 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kevin Foster, MD principal investigator

Arizona Burn Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing rThrombin, 1000 IU/mL in people with Blood Loss, Surgical, run by ZymoGenetics at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Death, Serious Adverse Events, Treatment-related Adverse Events (AE), AEs Leading to Discontinuation, and AEs of Hypersensitivity (time frame: Days 1 through 29, continuously). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00859547, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2012.