Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

Phase 3

Completed

Conditions: Spinal Surgery
Vascular Surgery

Interventions: Biological: rThrombin

Registration Number: NCT00491608

Lead Sponsor: ZymoGenetics

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 234

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	rThrombin	rThrombin

Primary Outcome Measures

Name	Time	Method
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	At Day 29	Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Death as Outcome, Serious Adverse Events, Treatment-related Adverse Events (AEs), and Treatment-emergent AEs	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.
Number of Participants With Abnormal Hematology Laboratory Results of Common Terminology Criteria (CTC) Grade 2 or Higher at Baseline and Day 29	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.
Number of Participants With Elevations in Coagulation Parameters of CTC Grade 3 or Higher at Baseline and Day 29	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.
Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29	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.
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	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.