Observational Study Assessing the Impact of Exposure to THROMBIN-JMI® on Coagulation Parameters.

Condition(s) targeted: Blood Coagulation

Phase: N/A

Status: Recruiting

Sponsored by: King Pharmaceuticals

Official(s) and/or principal investigator(s):
Craig A. Paterson, MD, MBA, Study Director, Affiliation: Medical Affairs

Overall contact:
Leslie Jones, Phone: 512-450-6179

The purpose of this study is to assess the effect of possible exposure to THROMBIN JMI® on activated partial thromboplastin time (aPTT) at 48 hours post surgery in subjects with likelihood of prior exposure to THROMBIN JMI® within the past 4 years.

Official title: A Phase 4, Multicenter, Open-Label, Observational Study Assessing the Impact of Exposure to THROMBIN-JMI® (Thrombin, Topical U.S.P [Bovine Origin]) on Coagulation Parameters

Study design: Cohort, Prospective

Primary outcome: Mean change from Baseline in aPTT at 48 hours post surgery

Secondary outcome: Changes from Baseline in specified antibody levels at 48 hours, 4 weeks, and 8 weeks post-surgery

Detailed description: This study is intended to observe the effects of possible repeat exposure to topical THROMBIN-JMI® on aPTT. Adult men and women who are scheduled to undergo qualified surgeries (defined as surgeries likely to require the use of an active topical hemostatic agent, but not likely to require transfusion of plasma), and who complete the informed consent process, and who meet all of the inclusion criteria and none of the exclusion criteria will be eligible for the study. As an observational study any decisions regarding the necessity for treatment to achieve hemostasis with this hemostatic product as an aid for perioperative hemostasis will be determined by the surgeon based upon the individual subject's condition.

Consequently, several assumptions and estimations are made in the design of the study. It is assumed that 20% of enrolled subjects will have pre-surgery bovine thrombin antibodies, and that 60% will receive THROMBIN JMI® during the study surgery, resulting in approximately 75 subjects in the primary study cohort and 195 subjects in the primary reference cohort. The primary endpoint of aPTT is chosen as prolongation beyond the normal reference range indicates either a factor deficiency or presence of an inhibitor. The latter is identified by either no correction or partial correction during mixing studies. At 48 hours post potential secondary exposure the secondary immune response should be sufficiently mounted as to see any impact of neutralizing antibodies on the aPTT.

After completion of the study surgeries, subjects will be categorized into cohorts based on whether their pre-surgery plasmas had or did not have anti-topical bovine thrombin antibodies and whether the subject received or did not receive THROMBIN JMI® intraoperatively. The primary study cohort will be subjects with anti-topical bovine thrombin antibodies pre-surgery, who received THROMBIN JMI® during the study surgery. The primary reference cohort will be those subjects with no anti-topical bovine thrombin antibodies pre-surgery and who did not receive THROMBIN JMI® during the study surgery. Antibody assessments will be not be performed until the end of the study for all subjects.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

To be eligible for this study, a subject MUST meet the following inclusion criteria:

- Must have undergone any one (or more) of the following surgical procedures within the

past 4 years, but not less than 30 days before the study surgery: lumbar/cervical discectomy, lumbar/cervical laminectomy, microdiscectomy, shunt procedures, craniotomy, peripheral nerve surgical procedures, carotid artery surgery, repair of aneurysm, hip or other joint replacement, open repair of bone fracture, open spine procedures, creation of dialysis access, lower or upper extremity vascular bypass, skin grafting, burn wound debridement, facelift, abdominoplasty;

- Must be scheduled to undergo any one of the following surgical procedures, which is

likely to require the use of topical thrombin, but is unlikely to require allogenic blood transfusion: lumbar/cervical discectomy, lumbar/cervical laminectomy, microdiscectomy, shunt procedures, craniotomy, peripheral nerve surgical procedures, carotid artery surgery, repair of aneurysm, hip or other joint replacement, open repair of bone fracture, open spine procedures, creation of dialysis access, lower or upper extremity revascularization, skin grafting, burn wound debridement, facelift, abdominoplasty;

- Must be 18 years of age or older;

- Must be capable and willing to provide written informed consent.

Exclusion Criteria:

To be eligible for this study, a subject MUST NOT meet any of the following exclusion criteria:

- Clinical history or clinical laboratory evidence of prior sensitivity to topical

bovine thrombin, any of its components and/or other materials of bovine origin;

- A female who is pregnant, nursing, or of childbearing potential while not practicing

effective contraceptive methods and women who have been on hormonal contraceptives within 30 days of the surgical procedure;

- Medical condition or personal circumstances that will prevent participation in and

completion of the follow-up visits at 48 hours, 4 weeks, and 8 weeks post-surgery;

- Currently participating in or has participated in (within 30 days prior to inclusion

in this trial) another clinical trial of an investigational drug, biologic, device, or procedure;

- Known hematologic or medical condition that impedes/prolongs coagulation;

- Screening fibrinogen level less than the lower limit of normal based on the local

laboratory ranges;

- Proposed exposure during the trial or previous known exposure to topical thrombin

other than THROMBIN-JMI®;

- Prothrombin time, aPTT or TT outside of normal reference values at Baseline (e. g.,

Screening Visit).

- Planned use of therapeutic doses of intravenous heparin or low molecular weight

heparin within 48 hours following surgery;

- Use of warfarin (Coumadin) within 5 days prior to surgery, or within 48 hours after

surgery.

Leslie Jones, Phone: 512-450-6179

Birmingham, Alabama, United States; Recruiting

Mobile, Alabama, United States; Recruiting

Tucson, Arizona, United States; Recruiting

Little Rock, Arkansas, United States; Recruiting

Glendale, California, United States; Recruiting

Arcadia, California, United States; Recruiting

Pasadena, California, United States; Recruiting

San Diego, California, United States; Recruiting

Miami, Florida, United States; Recruiting

Orlando, Florida, United States; Recruiting

Melbourne, Florida, United States; Recruiting

Boca Raton, Florida, United States; Recruiting

Springfield, Illinois, United States; Recruiting

Chicago, Illinois, United States; Recruiting

Fort Wayne, Indiana, United States; Recruiting

Muncie, Indiana, United States; Recruiting

Indianapolis, Indiana, United States; Recruiting

Lexington, Kentucky, United States; Recruiting

Louisville, Kentucky, United States; Withdrawn

Shreveport, Louisiana, United States; Recruiting

Salisbury, Maryland, United States; Recruiting

Springfield, Massachusetts, United States; Recruiting

Grand Blanc, Michigan, United States; Recruiting

Flint, Michigan, United States; Recruiting

Detroit, Michigan, United States; Recruiting

Saginaw, Michigan, United States; Completed

Royal Oak, Michigan, United States; Recruiting

Jackson, Mississippi, United States; Recruiting

Kansas City, Missouri, United States; Completed

Billings, Montana, United States; Recruiting

Las Vegas, Nevada, United States; Withdrawn

Hackensack, New Jersey, United States; Recruiting

Manhasset, New York, United States; Recruiting

New York City, New York, United States; Recruiting

Winston-Salem, North Carolina, United States; Recruiting

Chapel Hill, North Carolina, United States; Recruiting

Toledo, Ohio, United States; Recruiting

Akron, Ohio, United States; Recruiting

Oklahoma City, Oklahoma, United States; Recruiting

Sewickley, Pennsylvania, United States; Recruiting

Pittsburgh, Pennsylvania, United States; Recruiting

Houston, Texas, United States; Recruiting

Temple, Texas, United States; Recruiting

Austin, Texas, United States; Withdrawn

Fort Worth, Texas, United States; Recruiting

Tyler, Texas, United States; Withdrawn

Morgantown, West Virginia, United States; Recruiting

Starting date: November 2008
Ending date: November 2009
Last updated: August 18, 2009