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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Rosacea

Intervention / Treatment
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* Device: KTP laser
* Drug: Ivermectin 1% cream


Participation Criteria
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Eligibility Criteria
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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

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 within-patient (split-face) random allocation
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laser and cream<br> | Device: KTP laser<br>* 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.<br>Drug: Ivermectin 1% cream<br>* Application of ivermectin 1% cream 1x/day. Interruption for 4 days in case of irritation/redness.<br>|
| Active Comparator: Laser alone<br> | Device: KTP laser<br>* 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.<br>|

What is the study measuring?
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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 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 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ivermectin, Rosacea, Laser