- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00491608
Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis
January 11, 2012 updated by: ZymoGenetics
A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin (rThrombin) in Surgical Hemostasis
The purpose of this study is to evaluate the safety and immune system response to recombinant thrombin when used to control bleeding in spinal and vascular surgery.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is a Phase 3b, open-label, single-group, multisite safety and immunogenicity study of recombinant thrombin (rThrombin) in participants who are at least 18 years of age and undergoing spinal or vascular surgery.
Eligible participants will receive topical rThrombin during surgery and complete a 1-month follow-up visit.
Study Type
Interventional
Enrollment (Actual)
234
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Pasadena, California, United States, 91105
- Huntington Memorial Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Currently undergoing cervical, thoracic, or lumbar discectomy; corpectomy, laminectomy, lateral or interbody fusion, including both anterior and posterior approaches (not including minimally invasive procedures; arterial reconstruction; peripheral artery bypass (PAB) grafting; or arteriovenous (AV) vascular access procedures
- History of surgery with high likelihood of exposure to bovine thrombin within the past 3 years. Prior surgery must have been 1 of the following open procedures: open procedures involving the spine or cranium, PAB grafting, AV vascular access procedures, autologous skin grafting, or other surgical procedure accompanied by documented treatment with bovine thrombin
- Age of 18 years or younger at time of informed consent
- If female and of child-bearing potential: Negative pregnancy test result within 14 days prior to treatment
- Use of a medically accepted form of contraception from the time of informed consent to completion of all follow-up study visits, if sexually active male or a sexually active female of childbearing potential
- Signed IRB/independent ethics committee-approved informed consent document
Exclusion Criteria:
- Currently undergoing procedures requiring cardiopulmonary bypass or involving the aortic arch
- Known hypersensitivity to rThrombin or any of its components
- Presence of medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
- Breastfeeding
- Receipt of treatment with any experimental agent within 30 days of study enrollment or treatment
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
rThrombin
|
1000 U/mL applied directly or in combination with absorbable gelatin sponge or powder
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Anti-recombinant Thrombin (rThrombin) Product Antibodies at Day 29 in Participants With and Without Anti-bovine Thrombin Product Antibodies at Baseline
Time Frame: At Day 29
|
Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies.
|
At Day 29
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Death as Outcome, Serious Adverse Events, Treatment-related Adverse Events (AEs), and Treatment-emergent AEs
Time Frame: Day 1 (surgery) to Day 29 (end of study), continuously
|
AE=a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment.
SAE=an unfavorable medical event that results in death, persistent or significant incapacity, or drug dependency or abuse; is life-threatening, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Treatment-related=possibly, probably, or certainly related to study drug.
Treatment-emergent=onset on or after treatment start.
Grade (Gr) 1=mild, Gr 2=moderate, Gr 3=severe, Gr 4=life threatening/disabling, Gr 5=death.
|
Day 1 (surgery) to Day 29 (end of study), continuously
|
Number of Participants With Abnormal Hematology Laboratory Results of Common Terminology Criteria (CTC) Grade 2 or Higher at Baseline and Day 29
Time Frame: Baseline and Day 29 (end of study)
|
Hemoglobin, low (g/L): Grade 2=<100 Grade 3=<80; Grade 4=<65.
Platelets, low: Grade 2=<75*10^9/L; Grade 3=<50*10^9/L; Grade 4=<25*10^9/L.
Leukocytes, low: Grade 2=<3.0-2.0*10^9/L;
Grade 3=<2.0-1.0*10^9/L;
Grade 4=<1.0*10^9/L.
Lymphocytes, low: Grade 2=<0.8*10^9/L;
Grade 3=<0.5*10^9/L;
Grade 4=<0.2*10^9/L.
Neutrophils, low: Grade 2=<1.5*10^9/L;
Grade 3=<1.0*10^9/L;
Grade 4=<0.5*10^9/L.
Changes in hematocrit values observed were not graded for severity.
|
Baseline and Day 29 (end of study)
|
Number of Participants With Elevations in Coagulation Parameters of CTC Grade 3 or Higher at Baseline and Day 29
Time Frame: Baseline and Day 29 (end of study)
|
Activated partial thromboplastin time (aPTT) elevations: Grade 3=>2*upper limit of normal (ULN).
International normalized ratio(INR)elevations: Grade 3=>2*ULN.
Changes in prothrombin time were not graded for toxicity.
n=Number of participants with assessments available at that visit.
|
Baseline and Day 29 (end of study)
|
Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29
Time Frame: Baseline and Day 29 (end of study)
|
Abnormal laboratory findings were recorded as AEs when the investigator considered them to be clinically significant (eg, an unusual result for the surgical population or for an individual participant) or when they were associated with symptoms or required treatment or a change in patient management.
|
Baseline and Day 29 (end of study)
|
Number of Participants With Clinically Significant Changes in Mean Values for Vital Signs (Temperature, Systolic Blood Pressure, Diastolic Blood Pressure, Respiration Rate, Heart Rate) at Baseline and Day 29
Time Frame: Baseline and Day 29 (end of study)
|
Laboratory findings considered clinically significant by investigator when associated with symptoms, required specific treatment, or required a change in participant management.
Clinically significant changes in vital signs were reported as adverse events.
|
Baseline and Day 29 (end of study)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Allan Alexander, MD, CPI, ZymoGenetics
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Randleman CD Jr, Singla NK, Renkens KL, Souza S, Pribble JP, Alexander WA. Persistence of antibodies to the topical hemostat bovine thrombin. J Am Coll Surg. 2010 Dec;211(6):798-803. doi: 10.1016/j.jamcollsurg.2010.07.023. Epub 2010 Oct 25.
- Singla NK, Ballard JL, Moneta G, Randleman CD Jr, Renkens KL, Alexander WA. A phase 3b, open-label, single-group immunogenicity and safety study of topical recombinant thrombin in surgical hemostasis. J Am Coll Surg. 2009 Jul;209(1):68-74. doi: 10.1016/j.jamcollsurg.2009.03.016. Epub 2009 May 28.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2007
Primary Completion (Actual)
July 1, 2008
Study Completion (Actual)
July 1, 2008
Study Registration Dates
First Submitted
June 22, 2007
First Submitted That Met QC Criteria
June 25, 2007
First Posted (Estimate)
June 26, 2007
Study Record Updates
Last Update Posted (Estimate)
January 13, 2012
Last Update Submitted That Met QC Criteria
January 11, 2012
Last Verified
January 1, 2012
More Information
Terms related to this study
Other Study ID Numbers
- 499F04
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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