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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00600483

Enrollment

1502

Registered

2008-01-25

Start date

2007-12-31

Completion date

2010-09-30

Last updated

2022-05-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiac Surgery, Sternal Wound Infection

Keywords

obesity, diabetes

Brief summary

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.

Detailed description

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.

Interventions

DRUGgentamicin-collagen sponge dipped in saline

100-cm2 sponge

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Surgical Wound Infections From Surgery Through Post-operative Day 90	90 days post cardiac surgery	Efficacy will be evaluated by a comparison between the 2 study groups of the incidence of surgical wound infections that occur within the period from surgery through postop day 90.

Secondary

Measure	Time frame	Description
Proportion of Patients With Deep Surgical Wound Infections Based on Centers for Disease Control Criteria Adjudicated by an Independent Blinded Committee.	90 days post cardiac surgery	—
Proportion of Patients With Superficial Surgical Wound Infections Based on Centers for Disease Control Criteria Adjudicated by an Independent Blinded Committee.	90 days post cardiac surgery	—
Surgically Treated Surgical Wound Infection Postoperative Day 90	90 days post cardiac surgery	Proportion of patients with surgically treated surgical wound infection adjudicated by an independent blinded committee.
ASEPSIS Score	90 days post cardiac surgery	ASEPSIS Score through 90 days postoperative - To compare antibiotic regimens for their effectiveness in preventing or treating wound sepsis, well-defined criteria for outcome are needed. A method of assessing wound healing has been devised that defines carefully the characteristics to be considered and how they are to be awarded points. Objective criteria are also included in the assessment. Points are given for the need for Additional treatment, the presence of Serous discharge, Erythema, Purulent exudate, and Separation of the deep tissues, the Isolation of bacteria, and the duration of inpatient Stay (ASEPSIS). The higher the points the worse outcome. Maximum Points would be 60. Minimum points would be 0
Rehospitalization for Sternal Wound Infection	90 days post cardiac surgery	Rehospitalization for Sternal Wound Infection - within 90 days postoperatively.
Number of Participants Positive for Each Pathogen Culture	90 days post cardiac surgery	Analysis associated with Microbial Pathogens in Adjudicated 90 Day SWI Subjects ME within Per Protocol Population. Any Microbial Pathogens Detected in SWI (ME)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Gentamicin Group Insertion of 2 gentamicin-collagen sponges between the sternal halves before closure of the sternotomy gentamicin-collagen sponge dipped in saline: 100-cm2 sponge	753
Control Group Standard of care, ie, insertion of no gentamicin-collagen sponge.	749
Total	1,502

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	26	47
Overall Study	Randomized but not treated	10	0

Baseline characteristics

Characteristic	Control Group	Total	Gentamicin Group
Age, Continuous	64.3 Years STANDARD_DEVIATION 10.5	64.3 Years STANDARD_DEVIATION 10.19	64.3 Years STANDARD_DEVIATION 9.88
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	10 Participants	5 Participants
Race (NIH/OMB) Black or African American	59 Participants	115 Participants	56 Participants
Race (NIH/OMB) More than one race	1 Participants	5 Participants	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	683 Participants	1371 Participants	688 Participants
Sex: Female, Male Female	219 Participants	442 Participants	223 Participants
Sex: Female, Male Male	530 Participants	1060 Participants	530 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	19 / 743	27 / 759
other Total, other adverse events	741 / 743	757 / 759
serious Total, serious adverse events	269 / 743	290 / 759

Outcome results

Primary

Number of Participants With Surgical Wound Infections From Surgery Through Post-operative Day 90

Efficacy will be evaluated by a comparison between the 2 study groups of the incidence of surgical wound infections that occur within the period from surgery through postop day 90.