Clinical trial NCT00245336: Study of Recombinant Human Thrombin for Bleeding During Surgery
Official title: A Phase 3, Randomized, Double-Blind, Controlled, Comparative Efficacy and Safety Study of Topical Recombinant Human Thrombin (rhThrombin) and Thrombin-JMI (Bovine Thrombin) in Surgical Hemostasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Surgical Hemostasis
Keywords: hemostasis
surgery
hemostatics
randomized controlled trial
phase 3
Lead sponsor: ZymoGenetics
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether recombinant human Thrombin (rhThrombin) is effective in stopping bleeding during surgery, in comparison with bovine thrombin.

Detailed description: This is a Phase 3 multiple site, randomized, double-blind, controlled trial designed to evaluate the comparative efficacy and safety of rhThrombin and bovine thrombin in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access.

After establishing eligibility, subjects will be randomized in a 1:1 ratio to receive rhThrombin (1000 U/mL) or bovine thrombin (1000 U/mL). During a surgical procedure, study participants will be treated with blinded study drug (rhThrombin or bovine thrombin) in combination with an absorbable gelatin sponge at appropriate bleeding evaluation site(s) and time to hemostasis (TTH) will be assessed for up to 10 minutes. Bleeding appropriate for TTH evaluation is defined as mild to moderate bleeding, either on its own or remaining after brisk bleeding has been controlled by standard surgical modalities. Blinded study drug may also be used at additional appropriate bleeding sites. Study participants will have follow-up visits at about 2 days and 1 month after surgery. Approximately 400 to 600 patients will participate in the study. The final sample size will be determined based on blinded interim results.

Eligibility criteria: Inclusion Criteria:

* Subject is undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access

Exclusion Criteria:

* Subject has undergone a therapeutic surgical procedure within 30 days prior to surgery
* Subject has history of heparin-induced thrombocytopenia
* Subject has known antibodies or hypersensitivity to thrombin or other coagulation factors or known sensitivity to other components of the study treatment
* Subject has received blood products within 24 hours prior to surgery

Primary outcomes:
measure: Time to hemostasis, as measured by the incidence of hemostasis within 10 minutes
timeFrame: 10 minutes
Secondary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Up to 29 days
measure: Incidence and grade of clinical laboratory abnormalities
timeFrame: Up to 29 days
measure: Incidence of anti-product antibodies
timeFrame: Up to 29 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardio Thoracic Surgeons, P.C.
state: Alabama
city: Birmingham
country: United States
facility: Cardio Thoracic Surgeons, P.C., Medical Center East / Baptist Montclair
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Arcadia
country: United States
facility: Methodist Hospital
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California, Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: University of Southern California, Keck School of Medicine
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Pensacola
country: United States
facility: Baptist Clinical Research
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern University Vascular Surgery
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Spine Group
state: Indiana
city: Lexington
country: United States
facility: Bluegrass Orthopedics/Bluegrass Musculoskeletal Research
state: Kentucky
city: Baton Rouge
country: United States
facility: Vascular Surgery Associates
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Abdominal Transplant
state: Louisiana
city: Detroit
country: United States
facility: VAMC Clinical Research Center
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: University of North Texas Science Center at Fort Worth
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: Murray
country: United States
facility: Physician's Research Options, LLC/The Intermountain Spine Institute
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: ZymoGenetics
name: Thomas C Reynolds, MD, PhD
role: STUDY_DIRECTOR
affiliation: Washington University School of Medicine
name: William Chapman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana Spine Group
name: Kenneth Renkens, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Fred Weaver, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weaver FA, Lew W, Granke K, Yonehiro L, Delange B, Alexander WA; Study Investigators. A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures. J Vasc Surg. 2008 Jun;47(6):1266-73. doi: 10.1016/j.jvs.2008.01.034. Epub 2008 Apr 28.
citation: Chapman WC, Singla N, Genyk Y, McNeil JW, Renkens KL Jr, Reynolds TC, Murphy A, Weaver FA. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007 Aug;205(2):256-65. doi: 10.1016/j.jamcollsurg.2007.03.020. Epub 2007 Jun 27.