Potassium-titanyl Phosphate (KTP) Laser vs KTP Laser and Ivermectin Cream for Facial Rosacea (KIR)

Comparison of the Efficacy of Potassium-titanyl Phosphate (KTP) Laser vs KTP Laser Combined With Ivermectin 1% Cream for Facial Rosacea: a Randomized Split-face Trial

Rosacea is a frequent chronic inflammatory disease affecting mainly the face but also eyes and scalp. Rosacea is classified into 3 types: erythemato-teleangiectatica, papulopustulosa and phymatosa. Treatments depend on the type and include topical and systemic antibiotics, azelaic acid, topical ivermectin, topical brimonidine, systemic isotretinoin as well as intense pulsed light (IPL) and laser therapies.

For treatment of telangiectasia and redness, laser and IPL therapies are the first choice. Vascular lasers, such as pulsed dye lasers (PDL) and potassium-titanyl phosphate (KTP) lasers as well as IPL, have demonstrated good efficacy in reduction of erythema and telangiectasias in patients with rosacea. However, these treatments are expensive and mostly not covered by the health insurance. Therefore, for patients it is important to receive the maximal effect and improvement after each single laser session.

Ivermectin is a semi-synthetic derivative of avermectin and has an anti-inflammatory effect as well as an antiparasitic effect on demodex mite. The latter is playing an important pathogenetic role in rosacea.

This randomized controlled study aims to compare the effect of KTP laser in combination with ivermectin 1% cream vs KTP laser alone in patients with facial rosacea.

Study Overview

• Status: Completed
• Conditions: Rosacea
• Intervention / Treatment: Device: KTP laser; Drug: Ivermectin 1% cream

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of dermatology, University Hospital Inselspital, Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fitzpatrick skin type I-IV
• Presence of facial erythematous rosacea or mild papulopustular rosacea with permanent erythema
• Informed consent signed

Exclusion Criteria:

• History of adverse events related to KTP laser therapy
• Pregnant or breastfeeding women
• Intention to become pregnant during the course of the study
• History of intolerance or allergic reaction to ivermectin 1% cream or one of the ingredients
• Ongoing treatment for skin cancer
• Ongoing treatment with strong inhibitors of P-glycoprotein (P-gp) and CYP3A4 (e.g., itraconazole, voriconazole, posaconazole, clarithromycin, cobicistat)
• Ongoing treatment with substances with a narrow therapeutic range whose excretion depends substantially on P-gp (e.g. digoxin, ciclosporin)
• Inability to understand the study content

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laser and cream	Device: KTP laser; Treatment with KTP 532 nm laser. Laser fluence depends on erythema intensity and ranges from 7.0 J/cm2 to 11 J/cm2 with a 4-11 mm spot size and 8-12 ms pulse duration.; Drug: Ivermectin 1% cream; Application of ivermectin 1% cream 1x/day. Interruption for 4 days in case of irritation/redness.
Active Comparator: Laser alone	Device: KTP laser; Treatment with KTP 532 nm laser. Laser fluence depends on erythema intensity and ranges from 7.0 J/cm2 to 11 J/cm2 with a 4-11 mm spot size and 8-12 ms pulse duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of laser and cream vs laser alone in reducing erythema as assessed by NEI	Any relative decrease of erythema on the side treated with KTP laser and ivermectin 1% cream vs laser alone as assessed by Normalized Erythema Index (NEI), ranging from 0 to 80, with higher values indicating a worst erythema.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of laser and cream vs laser alone in reducing erythema as assessed by SRI	Any relative decrease of erythema on the side treated with KTP laser and ivermectin 1% cream vs laser alone as assessed by Skin Redness Index (SRI), ranging from 1 to 4, with higher score indicating a worst erythema.	16 weeks
Efficacy of laser and cream vs laser alone in reducing erythema as assessed by CEA	Any decrease of erythema on the side treated with KTP laser and ivermectin 1% cream vs laser alone as assessed by Clinical Erythema Assessment (CEA), ranging from 0 to 4, with higher score indicating a worst erythema.	4, 8, 12, 16 weeks
Efficacy of laser and cream vs laser alone in the clinical improvement of skin lesions as assessed by PGA	Any change of skin lesions on the side treated with KTP laser and ivermectin 1% cream vs laser alone as assessed by 6-point Physician Global Assessment (PGA), ranging from 0 to 5, with higher score indicating a better outcome.	4, 8, 12, 16 weeks
Patient's satisfaction related to laser and cream vs laser alone in the improvement of skin lesions as assessed by VAS	Any difference of patient's satisfaction for the improvement of skin lesions on the side treated with KTP laser and ivermectin 1% cream vs laser alone as assessed by a 9-point anchored visual analogue scale (VAS), ranging from -4 to +4, with negative scores indicating a worsening of condition, with 0 indicating no difference and with positive scores indicating an improvement.	4, 8, 12, 16 weeks
Efficacy of laser and cream vs laser alone in reducing papules and papulopustules	Any change in the number of papules and papulopustules on the side treated with KTP laser and ivermectin 1% cream vs laser alone.	4, 8, 12, 16 weeks
Efficacy of laser and cream vs laser alone in reducing telangiectasia severity as assessed by TGS	Any change of telangiectasia severity on the side treated with KTP laser and ivermectin 1% cream vs laser alone as assessed by telangiectasia grading scale (TGS), ranging from 0 to 3, with higher score indicating a worst telangiectasia severity.	4, 8, 12, 16 weeks
Efficacy of laser and cream vs laser alone in reducing face swelling as assessed by the patient	Any change in the number of days of face swelling on the side treated with KTP laser and ivermectin 1% cream vs laser alone, as assessed by the patient	4, 8, 12, 16 weeks
Efficacy of laser and cream vs laser alone in reducing face redness as assessed by the patient	Any change in the number of days of face redness on the side treated with KTP laser and ivermectin 1% cream vs laser alone, as assessed by the patient.	4, 8, 12, 16 weeks
Efficacy of laser and cream vs laser alone in reducing face purpura as assessed by the patient	Any change in the number of days of face purpura on the side treated with KTP laser and ivermectin 1% cream vs laser alone, as assessed by the patient.	4, 8, 12, 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of observed side-effects	Cumulative number of observed treatment side-effects.	16 weeks
Incidence of observed adverse events	Cumulative number of observed treatment adverse events.	16 weeks

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Kristine Heidemeyer, MD, University Hospital Inselspital, Bern

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2023
• Primary Completion (Actual): November 1, 2024
• Study Completion (Actual): November 1, 2024

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: September 4, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Rosacea; Ivermectin; Laser
• Additional Relevant MeSH Terms: Skin Diseases; Rosacea; Anti-Infective Agents; Antiparasitic Agents; Ivermectin
• Other Study ID Numbers: 2023-D0015

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