Clinical Trial of a Silver Eluting Dressing System

Rationale:

One of the most common post-operative complications of surgical procedures remains surgical
site infection, which causes significant morbidity and healthcare costs (estimated at $1.5
billion per year) among hospitalized patients. Surgical wounds for lower extremity
revascularization are particularly prone to infection and dehiscence, with rates in some
series as high as 44%(Kent, Bartek et al. 1996). Currently, the Guideline for Prevention of
Surgical Site Infection recommends the use of sterile dressing to protect closed incisions
for 24 to 48 hour postoperatively. However, no evidence-based recommendations are made with
regards to dressing types for use in post-operative incision care.

A plethora of wound dressings are available in the market, with silver-based dressing among
these recent innovations. Topical silver treatment is an effective bactericidal agent that
does not induce bacterial resistance when used in therapeutic levels. Acticoat
Absorbent®(Smith and Nephew, Inc.), an antimicrobial barrier dressing is coated with
nanocrystalline silver that delivers a controlled, sustained (up to three days) dose of
silver ions. Additionally, this dressing absorbs moisture (minimizing wound maceration), and
is safe and effective against a broad range of microorganisms. Acticoat Absorbent®
(Acticoat) is indicated for surgical wounds, chronic wounds, and burn wounds; however, data
are lacking regarding in its potential role in postoperative surgical incision wound
infection prophylaxis.

The Principal Investigator recently completed a non-concurrent, single-institution study of
patients who received conventional non-silver containing dressing with Acticoat as
post-operative dressing following defined lower extremity revascularizations(Childress,
Berceli et al. 2007). The study population comprised 216 patients who underwent 248 cases
that met inclusion criteria. Both groups were similar with regards to age at the time of
first procedure, gender, race, diabetes, hypertension, current smoking, and renal
insufficiency (creatinine >1.5 mg/L). Furthermore, both groups had tissue loss as the most
common indication for the lower extremity revascularization procedure, with 47% (55/118) for
the control group and 38% (49/130) for the treatment group. Moreover, autogenous vein bypass
graft was the most common procedure performed for the control (65/118, 55% of procedures)
and treatment (54/130, 42% of procedures) groups.

The surgeons and other providers found the dressing regimen easy to apply and care for
post-operatively. Revascularization pulses could be palpated through the dressing, and the
low profile permitted identification of post-operative soft tissue changes such as
hematomas. Compressive ace bandages could be applied without disturbing the original
dressing.

Regarding the primary findings, no substantial dressing material specific complications were
noted, including no apparent allergic reactions. The wound complication rate for the control
group was 14% (17/118), and for the treatment group was 5% (7/130). Over the intervention
phase, the wound overall complication rate fell by 64% (c2 = 5.76, df = 1, p = 0.016).

These findings provide clinical evidence that an Acticoat based dressing system offers a
potentially efficacious, cost-effective adjunct to reduce surgical site infections for lower
extremity revascularization. Based on this data, we believe that further investigation via
multi-center randomized clinical trial is warranted. Thus for the current proposal we
hypothesize that immediate application of Acticoat Absorbent® as a post-operative dressing
would reduce closed incisional wound complications in patients undergoing lower extremity
revascularizations involving infrainguinal skin incisions will result in a clinically
significant reduction in wound complication rates compared to standard non-silver eluting
dressing material.

Procedure:

- Patient randomized in OR after wound closure completed

- Wound closure technique at the discretion of the surgeon (Dermabond is a dressing and
can not be utilized)

- Final OR dressing is test (silver vs standard) dressing, secured per surgeon preference

- Original OR dressing stays in place until gross soiling impairs standard wound hygiene,
clinical need to remove, or POD#3, whichever comes first

- Subsequent dressings, wound care at the discretion of providers

- Visual wound checks at least at 2 and 4 weeks (+/- 5 days)

Clinical, economic, patient quality of life, and resource utilization data is then collected
at standard clinical encounters

Primary Endpoint: Any wound complication within 30 days

Power and Sample Size Calculations:

- Current endpoint rate at least 25%(Kent, Bartek et al. 1996; Nguyen, Brahmanandam et
al. 2007)

- Anticipate 10% absolute (40% relative) wound complication rate reduction(Childress,
Berceli et al. 2007)

- Power 0.8

- alpha 0.05

- control event rate of 0.25

- treatment event rate of 0.15

- 1:1 randomization

- -->total study sample size 250 per group (500 total).

Inclusion Criteria:

- Adult patient capable of informed consent who completes consent process

- Undergoing open (an incision below inguinal ligament) surgical procedure for
peripheral arterial vascular disease in which it is anticipated that the incisions
will be closed. Open cases combined with endovascular approaches acceptable.

Exclusion Criteria:

- Age less than 18

- Known allergy to silver or alginate

- Participation in another interventional clinical trial