Pilot Study to Compare Topical Voriconazole to Placebo as a Pain Reducing Agent

This single-center, prospective, randomized, double-blind, controlled pilot study conducted
at San Antonio Military Medical Center will evaluate the effectiveness of topical
voriconazole for pain relief at autogenous skin donor sites compared to a topical placebo
application. The patients will act as their own control. All participants and investigators
in the study will be blinded to the treatment arm utilized on each of the patient's donor
sites (voriconazole versus placebo). Patients, who are scheduled for skin grafting and have
met the inclusion criteria for this study, will be invited to enroll in the study. Only those
patients who have been planned for skin graft sites that are approximately symmetrical in
size will be allowed to enroll in the study. The donor site wounds will be studied using a
paired design consisting of voriconazole or the placebo applied topically to same-patient
matched donor sites. Patients will be queried via the pain assessment tool as to perceived
pain at timed intervals. Dialysate samples will be collected via microdialysis probes at
matching timed intervals in order to measure levels of oxidized linoleic acid metabolites
shown in previous studies to be present in peripheral nerves.

Inclusion Criteria:

1.1 Subject must be at least 18 years of age and no older than 60 years of age of either
gender and in good general health.

1.2 Subject has sustained burn wounds of less than 30 percent of the total body surface
area, in order to minimize the systemic effects on wound healing and the risk of infection
(both of which increase with increasing burn size).

1.3 Subject has sustained Burn or trauma/orthopedic wounds do not involve the harvesting
area.

1.4 Subject has sustained burn or trauma/orthopedic wounds that, in the judgment of the
attending surgeon, require excision and grafting of sufficient extent to justify two donor
sites of equal and symmetrical size on non-dependent body surfaces areas. Note: Only two
donor sites will be studied, however if the subject requires more than two donor sites,
they will not be excluded.

1.5 The scheduled excision and grafting procedure is the first such operation for the
subject during this hospitalization and injury.

1.6 Subject agrees to participate in follow-up evaluations (Post Op Day 0-3 and one follow
up appointment between Post Op day 30-45 for Donor site evaluation and photos of both donor
sites.

Exclusion Criteria:

2.1 Critical illnesses such as those requiring ventilator support, or having a systemic
infection or hemodynamic instability, defined as a mean arterial pressure less than 60 for
an extended period of time or requiring vasoactive medications to support blood pressure.

2.2 Patients unable to accurately communicate pain secondary to medical illness, altered
mental status, spinal cord injury, and known current narcotic drug use.

2.3 Patients unable to make his/her own decision for the informed consent. (Not seeking
consent from the legal authorized representative; self consent only).

2.4 Major acute or chronic medical illnesses that could affect wound healing (e.g.
peripheral vascular disease, blood clotting disorder).

2.6 Cellulitis or other infection of the potential donor sites.

2.7 Donor site has been previously harvested for grafting.

2.8 Donor site crosses a joint.

2.9 Any Corticosteroid use that could interfere with wound healing thus OLAM levels.

2.10 Subjects with greater than 30% total body surface area burns.

2.11 Pregnancy or lactation. (Beta HCG pregnancy test completed prior to operative
procedure, not part of study) In the event that we have a record of a hysterectomy, no
pregnancy test will be done, and the subject will be assumed NOT to be pregnant.

2.12 Prisoners.

2.13 Subjects having any contraindications for voriconazole. The contraindications are 1)
known hypersensitivity to voriconazole; and 2) Coadministration of terfenadine, astemizole,
cisapride, pimozide, quinidine or sirolimus, rifampin, carbamazepine, long acting
barbiturates, high dose ritonavir, rifabutin, ergotamine, dihydroergotamine, oral
contraceptives or St. John's Wort. A one week washout shall be determined for the above
listed medications prior to allowing entry into the study.