Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ZymoGenetics
ClinicalTrials.gov Identifier:
NCT00491608
First received: June 22, 2007
Last updated: January 11, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Spinal Surgery
Vascular Surgery
Biological: rThrombin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by ZymoGenetics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 234
Study Start Date: June 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
rThrombin
Biological: rThrombin
1000 U/mL applied directly or in combination with absorbable gelatin sponge or powder

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00491608

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

No publications provided by ZymoGenetics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ZymoGenetics
ClinicalTrials.gov Identifier: NCT00491608     History of Changes
Other Study ID Numbers: 499F04
Study First Received: June 22, 2007
Results First Received: November 3, 2011
Last Updated: January 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by ZymoGenetics:
Phase 3b
rThrombin
spine surgery
vascular surgery
hemostasis
immunogenicity
safety

Additional relevant MeSH terms:
Thrombin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014