Hypertrophic Scar Prevention by Novel Topical Gel Application

Phase 1

Terminated

Conditions: Hypertrophic Scar

Interventions: Drug: Pentamidine Isethionate
Drug: Placebo

Registration Number: NCT03403621

Lead Sponsor: Mayo Clinic

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Topical Pentamidine Isethionate	Pentamidine Isethionate	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).
Placebo Control	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Serious Adverse Events	4 weeks post-operatively	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 \[due to treatment\].

Secondary Outcome Measures

Name	Time	Method
Vancouver Scar Scale (VSS)	Baseline (preoperatively) and at weeks 2 and 4.	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.
Adverse Events	4 weeks post-operatively	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.
Change in Scar Fibrosis	Baseline (preoperatively) and 4 weeks post-operatively.	Semi-quantitative assessment of scar fibrosis on skin punch biopsy using a scale of none(1) - mild(2) - moderate(3) - severe(4)
Change in Scar Sclerosis	Baseline (preoperatively) and 4 weeks post-operatively.	Semi-quantitative assessment of scar sclerosis on skin punch biopsy using a scale of none(1) - mild(2) - moderate(3) - severe(4)
Change in Scar Volume	Baseline (pre-operatively) and at postop week 2 and 4.	Ultrasound will be used to quantify hypertrophic scar dimensions (length, width and height) and volume size using cm\^3 as the unit of measure.
Change in Scar Angioplasia	Baseline (preoperatively) and 4 weeks post-operatively.	Semi-quantitative assessment of scar angioplasia on skin punch biopsy using a scale of none(1) - mild(2) - moderate(3) - severe(4)
Change in Scar Relative Depth	Baseline (preoperatively) and 4 weeks post-operatively	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)
Change in Scar Absolute Depth	Baseline (preoperatively) and 4 weeks post-operatively	Measurement of scar absolute depth on skin punch biopsy reporting in millimeters (mm)
Patient Scar Assessment Scale (PSAS)	Baseline (preoperatively) and at weeks 2 and 4.	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).
Observer Scar Assessment Scale (OSAS)	Baseline (preoperatively), 2 weeks, and 4 weeks	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).