Hypertrophic Scar Prevention by Novel Topical Gel Application

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

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.

Study Overview

• Status: Terminated
• Conditions: Hypertrophic Scar
• Intervention / Treatment: Drug: Pentamidine Isethionate; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BMSO Research Team; Phone Number: 507-538-4849; Email: Hodge.Jessica@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical 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).	Drug: Pentamidine Isethionate; Approximately 1.8 mL single dose delivered as topical formulation containing 2% topical pentamidine in silicone-containing base.; Other Names: Pentamidine 2% cream
Placebo Comparator: Placebo Control; 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; No active ingredient. Approximately 1.8 mL single dose delivered as topical silicone compounding base only.; Other Names: PCCA Pracasil™-Plus (PP)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Alexander Meves, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2018
• Primary Completion (Actual): February 26, 2020
• Study Completion (Actual): February 26, 2020

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Fibrosis; Cicatrix; Hypertrophy; Cicatrix, Hypertrophic; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents; Pentamidine
• Other Study ID Numbers: 17-005230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No