Hypertrophic Scar Prevention by Novel Topical Gel Application

Study Overview
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Brief Summary
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Researchers are trying to find out more about the side effects of topical (applied to the skin) Pentamidine, to determine if it is safe for use in people. They also want to find out if topical use of Pentamidine can help treat hypertrophic scars. Pentamidine is a medicine that is currently used to treat certain kinds of infection. It is most often given by intravenous (into a vein) or inhalation (through a breathing device). This medication is approved by the U.S. Food and Drug Administration (FDA) for use in these forms. Everyone in this study will receive topical Pentamidine (TP) in a silicone based gel (PCCA Pracasil Plus). Topical treatment of Pentamidine is still experimental and has not been formally tested for safety or effectiveness in a randomized control trial within the United States. The FDA has allowed the use of topical Pentamidine in this research study.

Detailed Description
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This study will investigate Pentamidine isethionate, compounded in a silicone-containing base, as adjuvant therapy to surgical scar excision to prevent adverse scarring and enhance skin rejuvenation.

Official Title
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Double Blind, Single-Center, Randomized, Within Subject Placebo, Phase I Study Evaluating the Effects of Novel Topical Gel in Prevention of Hypertrophic Scar Formation

Conditions
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Hypertrophic Scar

Intervention / Treatment
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* Drug: Pentamidine Isethionate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of hypertrophic scar by a Mayo Clinic plastic surgeon or dermatologist. Target disease or condition: Hypertrophic scar Subject with a hypertrophic scar that meet all of the following criteria: Linear scar ≥5 to ≤40 cm in length Present for minimum 6 months Located anywhere in the body except on the face or front of neck Resulting from surgical or traumatic injury, or other scar considered appropriate for surgical excision Ability to safely undergo scar excision surgery Capacity to provide informed consent Ability to comply with protocol Subject is judged, by the clinical investigator, to be healthy as evidenced by lack of clinically significant abnormal findings on medical history, physical examination, electrocardiogram, vital signs, and clinical laboratory tests. Exclusion Criteria: Subjects identified as having a keloid or a scar not appropriate for surgical excision Subjects who are positive for hepatitis B surface antigen (HbsAg), hepatitis C antibody and HIV as determined in screening the subject's electronic medical record. Concurrent use of corticosteroids (including inhaled steroids), cyclooxygenase-2 (COX-2) inhibitors and/or drugs that are strong inhibitors and inducers of cytochrome P450 (CYP) enzymes Are immuno-compromised (HIV infected, cancer and other disease affecting the basal immune response) Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, hematological, or metabolic disease that is, in the opinion of the investigator, not stabilized or may otherwise impact the results of the study. Subjects with renal and hepatic impairment. Known allergy or hypersensitivity to the study drug(s) or one of the ingredients of the formulation. Any infection or wound in the area to treat including photosensitive dermatosis or inflammatory acne. Existence of any surgical, medical or laboratory condition that, in the judgment of the clinical investigator, might interfere with the safety, distribution, metabolism or excretion of the drug Participation in another clinical study in the past 30 days or concurrent participation in another clinical trial. Patients with poorly controlled diabetes mellitus (HbA1C ≥ 8%), peripheral neuropathy, or known concomitant vascular problems. Pregnant or lactating female patients. Prisoners. Subjects who smoke cigarettes and/or use other tobacco products.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will receive two treatments: drug and vehicle. Drug will be applied to one of two treatment sites. Vehicle will be applied to the other site. Treatment sites are distal and proximal end of the incision. Drug will be randomized to treatment site distal or proximal and masking will be as indicated. A 1-2 cm border zone will remain untreated in the middle of the scar.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical Pentamidine Isethionate<br>Subjects were randomly assigned to apply topical pentamidine isethionate to either the proximal or distal end of their incision every 48 hours for 4 weeks following surgical scar excision (14-16 treatments). | Drug: Pentamidine Isethionate<br>* Approximately 1.8 mL single dose delivered as topical formulation containing 2% topical pentamidine in silicone-containing base.<br>* Other names: Pentamidine 2% cream;|
| Placebo Comparator: Placebo Control<br>Subjects were randomly assigned to apply topical placebo to either the proximal or distal end of their incision every 48 hours for 4 weeks following surgical scar excision (14-16 treatments). The subject served as their own control. | Drug: Placebo<br>* No active ingredient. Approximately 1.8 mL single dose delivered as topical silicone compounding base only.<br>* Other names: PCCA Pracasil™-Plus (PP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events | Number of participants to experience serious adverse events as defined as death [due to treatment] or life threatening adverse experience [due to treatment], hospitalization [due to treatment], persistent or significant disability or incapacity [due to treatment], birth defect/anomalies [due to treatment] and tissue necrosis [due to treatment]. | 4 weeks post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants to experience adverse events as defined as skin infection, skin irritation and wound dehiscence. Skin irritation is scored by local skin reaction (LSR) grading scale. Wound infection is defined by skin that is red, swollen, hot and painful (calor, dolor, rubor, tumor) [by clinical exam] with or without discharge. Wound dehiscence is defined as a measurable breaking open of the surgical incision along the suture. | 4 weeks post-operatively | 
| Change in Scar Volume | Ultrasound will be used to quantify hypertrophic scar dimensions (length, width and height) and volume size using cm^3 as the unit of measure. | Baseline (pre-operatively) and at postop week 2 and 4. | 
| Change in Scar Fibrosis | Semi-quantitative assessment of scar fibrosis on skin punch biopsy using a scale of none(1) - mild(2) - moderate(3) - severe(4) | Baseline (preoperatively) and 4 weeks post-operatively. | 
| Change in Scar Sclerosis | Semi-quantitative assessment of scar sclerosis on skin punch biopsy using a scale of none(1) - mild(2) - moderate(3) - severe(4) | Baseline (preoperatively) and 4 weeks post-operatively. | 
| Change in Scar Angioplasia | Semi-quantitative assessment of scar angioplasia on skin punch biopsy using a scale of none(1) - mild(2) - moderate(3) - severe(4) | Baseline (preoperatively) and 4 weeks post-operatively. | 
| Change in Scar Relative Depth | Semi-quantitative assessment of scar relative depth on skin punch biopsy using a scale of Epidermis(1) - Mid-Reticular Dermis (2) - Deep Dermis(3) - Fat(4) | Baseline (preoperatively) and 4 weeks post-operatively | 
| Change in Scar Absolute Depth | Measurement of scar absolute depth on skin punch biopsy reporting in millimeters (mm) | Baseline (preoperatively) and 4 weeks post-operatively | 
| Vancouver Scar Scale (VSS) | The VSS assesses 4 variables: vascularity, height/thickness, pliability, and pigmentation. Scale ranges are as follows. Pigmentation (0=normal, 1=hypopigmentation, 2=hyperpigmentation). Height (0=flat, 1=less than 2 mm, 2=2 to 5 mm, 3=greater than 5 mm). Vascularity (0=normal, 1=pink, 2=red, 3=purple). Pliability (0=normal, 1=supple, 2=yielding, 3=firm, 4=banding,5=contracture). Total score can range from 0 to 13, with 0=normal skin, and 13=severe scarring. | Baseline (preoperatively) and at weeks 2 and 4. | 
| Patient Scar Assessment Scale (PSAS) | The patient scar scale assesses pain, itching, color, stiffness, thickness, and irregularity. The scale rates each variable on a scale from 1 (normal skin) to 10 (worst scar imaginable), with a total possible score ranging from 1 (normal) to 120 (worst scar imaginable). | Baseline (preoperatively) and at weeks 2 and 4. | 
| Observer Scar Assessment Scale (OSAS) | The observer scar assessment scale assesses vascularity, pigmentation, thickness, relief, pliability, and surface area. The scale rates each variable on a scale from 1 (normal skin) to 10 (worst scar imaginable), with a total possible score ranging from 1 (normal) to 120 (worst scar imaginable). | Baseline (preoperatively), 2 weeks, and 4 weeks |