Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

Vascular Surgery Clinical Trial

Official title:

A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin (rThrombin) in Surgical Hemostasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00491608
• Other study ID #: 499F04
• Status: Completed
• Phase: Phase 3
• First received: June 22, 2007
• Last updated: January 11, 2012
• Start date: June 2007
• Est. completion date: July 2008

Study information

• Verified date: January 2012
• Source: ZymoGenetics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 234
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Spinal Surgery
• Vascular Surgery

Intervention

Biological:
• rThrombin
1000 U/mL applied directly or in combination with absorbable gelatin sponge or powder

Locations

Country	Name	City	State
United States	Huntington Memorial Hospital	Pasadena	California

Sponsors (1)

Lead Sponsor	Collaborator
ZymoGenetics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies.	At Day 29	Yes
Secondary	Number of Participants With Death as Outcome, Serious Adverse Events, Treatment-related Adverse Events (AEs), and Treatment-emergent AEs	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	Yes
Secondary	Number of Participants With Abnormal Hematology Laboratory Results of Common Terminology Criteria (CTC) Grade 2 or Higher at Baseline and Day 29	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)	Yes
Secondary	Number of Participants With Elevations in Coagulation Parameters of CTC Grade 3 or Higher at Baseline and Day 29	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)	Yes
Secondary	Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29	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)	Yes
Secondary	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	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)	Yes