Safety and Efficacy of an Antibiotic Implant in Cardiac Surgical Subjects at Higher Risk for Sternal Wound Infection

A Randomized, Controlled, Phase 3 Study of Gentamicin-Collagen Sponge in Cardiac Surgical Subjects at Higher Risk for Sternal Wound Infection

The purpose of this study is to determine whether the gentamicin-collagen sponge is safe and effective in preventing sternal wound infections in patients undergoing cardiac surgery who are at a greater risk of developing sternal wound infections.

Sternal wound infection (SWI) is a significant problem in cardiac surgical subjects,in particular in those with risk factors such as diabetes and obesity. There is a long unmet need for an intervention that can reduce the incidence and severity of SWIs in high-risk subjects.

Gentamicin is an antibiotic that is effective in treating certain kinds of infection. Collagen is a protein that is found in all mammals. The gentamicin-collagen sponge is a thin flat sponge made out of collagen that comes from cow tendons and containing gentamicin. When inserted into a surgical site, the collagen breaks down and the gentamicin is released at the site but very little is absorbed into the blood stream. The high levels of antibiotic at the surgical site may prevent an infection at the surgical site.

Outside of the United States more than 3,500 subjects have received treatment in clinical studies with the gentamicin-collagen sponge, primarily for orthopedic, intraabdominal, and cardiothoracic surgeries or wound infections following surgical procedures or traumatic events.

In this study, all subjects will be given treatment that is normally given to prevent surgical infections. For subjects randomly assigned to the gentamicin-collagen sponge treatment group, 2 sponges will be placed between the sternal halves during surgery. IMMEDIATELY before insertion of the sponge the surgeon should wet the sponge with saline as shown in the training/certification document. This wet sponge SHOULD BE INSERTED INTO THE STERNUM WITHIN APPROXIMATELY 15 SECONDS (AFTER THIS TIME IT MAY BECOME MORE DIFFICULT TO HANDLE). All subjects will be followed for 90 days after surgery to determine whether they develop a sternal wound infection.

Inclusion Criteria:

• Scheduled to undergo nonemergent CABG and/or valve repair or replacement surgery through a full median sternotomy. This includes the following eligible procedures: isolated CABG surgery, isolated valve surgery, and combined CABG + valve surgery.
• Be at higher risk for SWI, defined as the presence of diabetes mellitus (treated with either oral agent or insulin) and/or obesity, defined as BMI > 30.
• Have the capacity to understand and sign an informed consent form.
• Are male or female and > 18 years of age.
• If female, be postmenopausal (no menstrual period for a minimum of 1 year), be surgically sterilized and have a negative serum or urine pregnancy test on entry in the study, or agree to use adequate birth control during the study and for 3 months after the administration of study agent. Medically acceptable contraceptives include: (1) approved hormonal contraceptives (such as birth control pills, Depo-Provera, or Lupron Depot), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, or (3) an intrauterine device (IUD).
• Agree to be available for evaluation from baseline until final evaluation at 90 days postsurgery.

Exclusion Criteria:

• Known history of hypersensitivity to gentamicin or bovine collagen.
• Undergoing emergency cardiac surgery (urgent surgery is allowed if informed consent is obtained and the study procedures can be performed).
• Undergoing a significant concomitant surgical procedure (eg, carotid endarterectomy, aortic root repair or replacement, DHCA, or pulmonary resection).
• Undergoing a minimally invasive or a thoracic surgical approach.
• Using a preoperative mechanical assist device or IABP if inserted for shock/low output syndrome (an IABP is allowed if it is inserted for unstable angina).
• Active and significant systemic infection, eg active endocarditis, or a history of significant recurrent systemic infection.
• Receiving antibiotic therapy within the 2 weeks before the date of surgery.
• Preoperative serum creatinine > 3 mg/dL or renal failure requiring dialysis.
• History of malignancy within the past year (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence).
• History of major organ transplantation, including bone marrow transplantation.
• Recent history of significant drug or alcohol abuse.
• Taking systemic immunosuppressive drugs, including steroids (at a dose > 10 mg oral prednisone daily) or a history of a current immunosuppressive condition (eg, symptomatic HIV infection), defined as a CD4 count < 200.
• Scheduled to receive "stress doses" of glucocorticoids (ie, doses > 2 mg/kg/day of methylprednisolone or equivalent).
• Pregnant, lactating, or of childbearing potential not practicing a birth control method with a high degree of reliability (defined in section 3.1).
• Postsurgical life expectancy ≤ 90 days, in the investigator's or sponsor's opinion.
• Refusal to accept medically indicated blood products.
• Current participation or participation within 30 days before the start of this study in another experimental drug or device study, or is currently participating in a study during which the administration of investigational drugs within 90 days is anticipated.
• Has a moderate or severe pectus deformity.