Clinical trial NCT00491608: Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis
Official title: A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin (rThrombin) in Surgical Hemostasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Surgery
Vascular Surgery
Keywords: Phase 3b
rThrombin
spine surgery
vascular surgery
hemostasis
immunogenicity
safety
Lead sponsor: ZymoGenetics
Sponsor class: INDUSTRY
First posted: 2007-06-26
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: At Day 29
Secondary outcomes:
measure: Number of Participants With Death as Outcome, Serious Adverse Events, Treatment-related Adverse Events (AEs), and Treatment-emergent AEs
timeFrame: Day 1 (surgery) to Day 29 (end of study), continuously
measure: Number of Participants With Abnormal Hematology Laboratory Results of Common Terminology Criteria (CTC) Grade 2 or Higher at Baseline and Day 29
timeFrame: Baseline and Day 29 (end of study)
measure: Number of Participants With Elevations in Coagulation Parameters of CTC Grade 3 or Higher at Baseline and Day 29
timeFrame: Baseline and Day 29 (end of study)
measure: Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29
timeFrame: Baseline and Day 29 (end of study)
measure: 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
timeFrame: Baseline and Day 29 (end of study)
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
Study officials:
affiliation: ZymoGenetics
name: Allan Alexander, MD, CPI
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.