Wound Healing Endpoint and Recurrence
Wound Healing Endpoint and Recurrence
This prospective pilot study is to enroll patients with clinically-defined infected wounds.
 Patients enrolled in the study will be followed for 16 weeks for wound closure (Phase A), and
 will then begin Phase B. 265 clinically diagnosed infected burn or chronic wound patients
 will be recruited for this study in Phase A. Based on the expectation that 89% of these
 wounds will heal within 16 weeks of enrollment, 234 of these patients will continue with the
 study for Phase B.
This prospective pilot study is to enroll patients with clinically-defined infected wounds.
 Patients enrolled in the study will be followed for 16 weeks for wound closure (Phase A), and
 will then begin Phase B. Wounds will be subjected to Standard of Care (SoC) followed by all
 Comprehensive Wound Center (CWC) wound physicians in the first 16 weeks. Trans - Epidermal
 Water Loss (TEWL) will be measured with a handheld, non-invasive device, the VapoMeter®
 Closed-Chambered device or using DermaLab TEWL probe. Both of these devices are used to read
 the device. They will be placed on the subjects skin and will read the TEWL measurement. When
 the device is placed on the skin, the measurement takes between 7-20 seconds with the
 standard adapter.

 Study visit 1 will include informed consent being signed, baseline information collected, 2
 biopsies will be collected unless the wound is not appropriate for biopsy or the patient
 chooses not to receive a biopsy then a swab for culture will be collected, wound image using
 a digital camera and Wound Vision Scout (a non-invasive, infrared imaging camera), and a
 quality of life survey will be completed by the subject. The patients medical chart will be
 followed for 16 weeks following visit 1. At 16 weeks (+/- 2 weeks) or within 10 days of wound
 closure whichever comes first, all subjects will return for study visit 2. If the target
 wound(s) is not yet healed at this visit, this visit will be part of their Standard of Care
 visit per the CWC. The patient's study participation will end at this visit but wound data
 will be collected, digital imaging of wound(s) and quality of life survey will be completed
 by the subject. If the target wound is determined by visual inspection to be healed at or
 prior to this visit, this will be a research only visit; the patient will continue to Phase
 B, a continuation of study visit 2. Various information will be collected on the data
 collection sheet, digital imaging and TEWL measurements will be recorded. The TEWL device
 will be placed on the skin. There will be 5 measurements obtained over the closed wound site.
 A reference (control) TEWL measurement will be taken from intact skin at an anatomically
 matched site on the patient.

 A high TEWL/ defective closure is defined as a TEWL value that equals 2 times the value of
 the patient's control measurement. Patients who meet this criterion will be randomized to one
 of four groups: EpiCeram treatment, Ceramiseal treatment, Vaseline treatment or no treatment.
 Patients randomized to a treatment group will be supplied with study product and will be
 instructed to apply twice daily to the closed wound site for the remaining weeks of the
 study. All High TEWL patients will be asked to return for Study Visits 3-6. Distribution of
 study product as applicable. For this study, a low TEWL/ adequate closure is defined as a
 value less than 2 times the value of the patient's control measurement. Patients who meet
 this criterion will not be randomized into a treatment group, but will continue to receive
 standard of care per their physician and will be asked to return for study visits 3, 4, and
 6. During these last visits the following activities will occur: TEWL measurements, digital
 imaging, sequential tape stripping to measure ceramide levels in the skin (up to 20 tape
 strips obtained). TEWL measurements will be obtained prior to tape stripping. The tape strips
 be completed after the TEWL measurements are obtained, wound site evaluation, various labs,
 medications review, distribution of study product (High TEWL only) and review of compliance
 and a quality of life survey is completed by the subject (visit 6 only).

 There may be some discomfort with the tissue biopsy procedure depending on the amount of
 sensation the subject has at the site of the wound and will be numbed by applying local
 anesthesia as appropriate to area being biopsied. The amount of pain that occurs with wound
 biopsies will vary from person to person, but all efforts will be made to minimize pain and
 is within the boundaries of the existing wound to avoid giving the patient a separate new
 wound. Bleeding is a possible complication, but the risk is low for the small biopsies and is
 reduced by using local anesthetics with epinephrine, and silver nitrate sticks are available
 in each patient room to cauterize biopsy sites as needed. Infection is also a potential risk;
 however, wound tissue biopsies are routinely performed as the standard of care in the CWC to
 diagnose wound infection. The biopsy site will be appropriately monitored for infection by
 the physician managing the wound during routine wound clinic visits.

 Possible risks for the use of the ceramide emulsion EpiCeram® are a temporary tingling
 sensation (10-15 minutes) and an extremely low risk of an allergic reaction. If this occurs
 the application of the cream will be stopped immediately. Possible risks for the use of
 Vaseline Petroleum and Ceramiseal™ are very low should be stopped if an allergic reaction
 occurs.There can be some minor redness and discomfort at the site of the tape stripping. The
 skin remains intact, i.e. the epidermis is not breached after the tape stripping procedure
 making this less than minimal risk. TEWL measurements are noninvasive and propose less than
 minimal risk.
Inclusion Criteria:

 -  Age ≥ 18

 -  Willing to comply with protocol instructions, including all biopsies, study visits and
 study activities.

 -  One of the following:

 1. Chronic wound of multiple etiologies and open for at least 30 days, including:

 1. Diabetic foot ulcers, Wagner grade 1-3

 2. Pressure ulcers, stage 2-3

 3. Venous leg ulcers, confirmed by venous duplex

 4. Burn wounds open

 5. Other etiology, deemed appropriate for biopsy

 2. Wounds not appropriate for biopsy due to either:

 1. Almost healed at the time of enrollment (per physician)

 2. Healed within 10 days prior to enrollment visit

 3. Clinical contraindication to biopsy in the opinion of the wound care
 provider

 -  Adequate arterial blood flow as evidenced by at least one of the following (for
 subjects receiving tissue biopsy, if would is located on a lower extremity below the
 knee):

 1. Transcutaneous oxygen measurement (TcOM) > 30 mmHg

 2. Ankle-brachial index ≥0.7

 3. Toe pressure > 30 mmHg

 Exclusion Criteria:

 -  Individuals who are deemed unable to understand the procedures, risks and benefits of
 the study, (i.e. unable to provide informed consent)

 -  Diabetics with Hemoglobin A1c > 10%

 -  Subjects with marked immunodeficiency (HIV/AIDS, organ transplant patients and cancer
 patients and patients with autoimmune disease on immunosuppressive medications).

 -  Wounds closed or to be closed by flap or graft coverage - including stage 4 pressure
 ulcers and Wagner grade 4 or 5 diabetic foot ulcers

 -  Prisoners

 -  Patients with allergies to petrolatum

 -  Patients who are currently enrolled in another research study which includes
 investigational treatment and/or medication