Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00491608
Recruitment Status : Completed
First Posted : June 26, 2007
Results First Posted : January 12, 2012
Last Update Posted : January 13, 2012
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Spinal Surgery Vascular Surgery Biological: rThrombin Phase 3

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  (Clinical Trial)
Actual Enrollment : 234 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin (rThrombin) in Surgical Hemostasis
Study Start Date : June 2007
Actual Primary Completion Date : July 2008
Actual Study Completion Date : July 2008

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U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Biological: rThrombin
1000 U/mL applied directly or in combination with absorbable gelatin sponge or powder

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00491608

United States, California
Huntington Memorial Hospital
Pasadena, California, United States, 91105
Sponsors and Collaborators
Study Director: Allan Alexander, MD, CPI ZymoGenetics

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: ZymoGenetics Identifier: NCT00491608     History of Changes
Other Study ID Numbers: 499F04
First Posted: June 26, 2007    Key Record Dates
Results First Posted: January 12, 2012
Last Update Posted: January 13, 2012
Last Verified: January 2012

Keywords provided by ZymoGenetics:
Phase 3b
spine surgery
vascular surgery

Additional relevant MeSH terms: