Hypertrophic Scar
Conditions
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.
Interventions
DRUGPentamidine Isethionate
Approximately 1.8 mL single dose delivered as topical formulation containing 2% topical pentamidine in silicone-containing base.
DRUGPlacebo
No active ingredient. Approximately 1.8 mL single dose delivered as topical silicone compounding base only.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Randomization will done by the Research Pharmacy
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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) |
| 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 Absolute Depth | Baseline (preoperatively) and 4 weeks post-operatively | Measurement of scar absolute depth on skin punch biopsy reporting in millimeters (mm) |
| 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. |
| 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). |
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants received two treatments: topical pentamidine isethionate and placebo. Participants were randomly assigned to apply topical pentamidine isethionate to either the proximal or distal end of their incision and placebo on the other end of their incision every 48 hours for 4 weeks following surgical scar excision (14-16 treatments).
Pentamidine Isethionate: Approximately 1.8 mL single dose delivered as topical formulation containing 2% topical pentamidine in silicone-containing base.
Placebo: No active ingredient. Approximately 1.8 mL single dose delivered as topical silicone compounding base only. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 35 years STANDARD_DEVIATION 15.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
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 \[due to treatment\].
Time frame: 4 weeks post-operatively
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical Pentamidine Isethionate | Serious Adverse Events | 0 Participants |
| Placebo Control | Serious Adverse Events | 0 Participants |
Secondary
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.
Time frame: 4 weeks post-operatively
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical Pentamidine Isethionate | Adverse Events | 4 Participants |
| Placebo Control | Adverse Events | 5 Participants |
Secondary
Change in Scar Absolute Depth
Measurement of scar absolute depth on skin punch biopsy reporting in millimeters (mm)
Time frame: Baseline (preoperatively) and 4 weeks post-operatively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topical Pentamidine Isethionate | Change in Scar Absolute Depth | -0.17 millimeters | Standard Deviation 2.26 |
| Placebo Control | Change in Scar Absolute Depth | 1.34 millimeters | Standard Deviation 2.09 |
Secondary
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)
Time frame: Baseline (preoperatively) and 4 weeks post-operatively.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Topical Pentamidine Isethionate | Change in Scar Angioplasia | 0 units on a scale |
| Placebo Control | Change in Scar Angioplasia | 0 units on a scale |
Secondary
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)
Time frame: Baseline (preoperatively) and 4 weeks post-operatively.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Topical Pentamidine Isethionate | Change in Scar Fibrosis | 1 units on a scale |
| Placebo Control | Change in Scar Fibrosis | 2 units on a scale |
Secondary
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)
Time frame: Baseline (preoperatively) and 4 weeks post-operatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Topical Pentamidine Isethionate | Change in Scar Relative Depth | 0 units on a scale |
| Placebo Control | Change in Scar Relative Depth | 0 units on a scale |
Secondary
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)
Time frame: Baseline (preoperatively) and 4 weeks post-operatively.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Topical Pentamidine Isethionate | Change in Scar Sclerosis | 0 units on a scale |
| Placebo Control | Change in Scar Sclerosis | 0 units on a scale |
Secondary
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.
Time frame: Baseline (pre-operatively) and at postop week 2 and 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topical Pentamidine Isethionate | Change in Scar Volume | Baseline, 2 weeks post-operative | -0.72 cm^3 | Standard Deviation 0.5 |
| Topical Pentamidine Isethionate | Change in Scar Volume | Baseline, 4 weeks post-operative | -0.65 cm^3 | Standard Deviation 0.77 |
| Placebo Control | Change in Scar Volume | Baseline, 2 weeks post-operative | -0.68 cm^3 | Standard Deviation 0.52 |
| Placebo Control | Change in Scar Volume | Baseline, 4 weeks post-operative | -0.76 cm^3 | Standard Deviation 0.52 |
Secondary
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).
Time frame: Baseline (preoperatively), 2 weeks, and 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topical Pentamidine Isethionate | Observer Scar Assessment Scale (OSAS) | Baseline | 32.3 score on a scale | Standard Deviation 12.8 |
| Topical Pentamidine Isethionate | Observer Scar Assessment Scale (OSAS) | 2 weeks | 23.5 score on a scale | Standard Deviation 10.1 |
| Topical Pentamidine Isethionate | Observer Scar Assessment Scale (OSAS) | 4 weeks | 23.2 score on a scale | Standard Deviation 8.6 |
| Placebo Control | Observer Scar Assessment Scale (OSAS) | Baseline | 31.2 score on a scale | Standard Deviation 13.7 |
| Placebo Control | Observer Scar Assessment Scale (OSAS) | 2 weeks | 23.3 score on a scale | Standard Deviation 13 |
| Placebo Control | Observer Scar Assessment Scale (OSAS) | 4 weeks | 26.3 score on a scale | Standard Deviation 9.9 |
Comparison: Baseline versus 2 weeksp-value: 0.21t-test, 2 sided
Comparison: Baseline versus 4 weeksp-value: 0.18t-test, 2 sided
Comparison: Baseline versus 2 weeksp-value: 0.33t-test, 2 sided
Comparison: Baseline versus 4 weeksp-value: 0.5t-test, 2 sided
Secondary
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).
Time frame: Baseline (preoperatively) and at weeks 2 and 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topical Pentamidine Isethionate | Patient Scar Assessment Scale (PSAS) | Baseline | 39 score on a scale | Standard Deviation 8.3 |
| Topical Pentamidine Isethionate | Patient Scar Assessment Scale (PSAS) | 2 weeks | 27.7 score on a scale | Standard Deviation 6.6 |
| Topical Pentamidine Isethionate | Patient Scar Assessment Scale (PSAS) | 4 weeks | 25.5 score on a scale | Standard Deviation 14.8 |
| Placebo Control | Patient Scar Assessment Scale (PSAS) | Baseline | 43.2 score on a scale | Standard Deviation 9.1 |
| Placebo Control | Patient Scar Assessment Scale (PSAS) | 2 weeks | 28.7 score on a scale | Standard Deviation 8.9 |
| Placebo Control | Patient Scar Assessment Scale (PSAS) | 4 weeks | 27.0 score on a scale | Standard Deviation 11.9 |
Comparison: Baseline versus 2 weeksp-value: 0.03t-test, 2 sided
Comparison: Baseline versus 4 weeksp-value: 0.08t-test, 2 sided
Comparison: Baseline versus 2 weeksp-value: 0.02t-test, 2 sided
Comparison: Baseline versus 4 weeksp-value: 0.007t-test, 2 sided
Secondary
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.
Time frame: Baseline (preoperatively) and at weeks 2 and 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topical Pentamidine Isethionate | Vancouver Scar Scale (VSS) | Baseline | 5.5 score on a scale | Standard Deviation 3.7 |
| Topical Pentamidine Isethionate | Vancouver Scar Scale (VSS) | 2 weeks | 4.0 score on a scale | Standard Deviation 2.2 |
| Topical Pentamidine Isethionate | Vancouver Scar Scale (VSS) | 4 weeks | 4.8 score on a scale | Standard Deviation 2.3 |
| Placebo Control | Vancouver Scar Scale (VSS) | Baseline | 4.8 score on a scale | Standard Deviation 3.6 |
| Placebo Control | Vancouver Scar Scale (VSS) | 2 weeks | 3.5 score on a scale | Standard Deviation 3.2 |
| Placebo Control | Vancouver Scar Scale (VSS) | 4 weeks | 5.8 score on a scale | Standard Deviation 2.2 |
Comparison: Baseline versus 2 weeksp-value: 0.42t-test, 2 sided
Comparison: Baseline versus 4 weeksp-value: 0.72t-test, 2 sided
Comparison: Baseline versus 2 weeksp-value: 0.51t-test, 2 sided
Comparison: Baseline versus 4 weeksp-value: 0.58t-test, 2 sided