Clinical trial NCT02761174: Topical Brimonidine to Reduce Inflammation After IPL-treatment in Patients With Facial Telangiectasias
Official title: Topical Brimonidine Reduces IPL-induced Erythema Without Affecting Efficacy: a Randomized Controlled Trial in Patients With Facial Telangiectasias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Telangiectasias
Keywords: Vascular lesions
inflammation
IPL
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: Skinperium, Christine Dierickx
name: Ellipse A/S Agern Allé 11, 2970 Hørsholm
First posted: 2016-05-04
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to investigate whether brimonidine cream can reduce IPL-induced inflammation in terms of redness, swelling and pain in patients with facial vascular lesions (telangiectasias). Furthermore, the effect of brimonidine cream on IPL-efficacy is evaluated one month after final IPL-treatment.

The hypothesis is that brimonidine, which has been proved effective in reduction of symptomatic erythema in patients with rosacea, also may have the ability to reduce IPL-induced erythema. Since the potential reduction in erythema is caused by vasoconstriction, brimonidine may further reduce IPL-induced oedema and pain.

Detailed description: Study design The study is designed as a dual-centre, randomized, intra-individual, split-face clinical controlled trial with blinded outcome assessment. A total of 20 patients with moderate to severe facial telangiectasias, without other clinical active dermatological disease in the skin, will be included. Severity and distribution (cheek, nose and chin) of telangiectasias must be symmetrical between facial sides in the individual patient at inclusion. All patients will receive IPL-treatments to both sides of the face. Before the first IPL-treatment, the left and right side of the face will be randomized to either brimonidine (Mirvaso) or only IPL-treatment and air-cooling (control), respectively. The study is conducted in an international collaboration between Bispebjerg Hospital, Department of Dermatology in Denmark and "Skinperium" private practice in Belgium.

Interventions Patients are asked to attend 3 treatment days and 2 follow-up visits. Treatment days are planed with 3 weeks intervals (± 5 days) and follow-up visits are planned at trial day 2 (one day after treatment day 1) and at 1 month (± 5 days) after the final treatment day. The consultations are estimated to last between half an hour and two hours. Patients are further asked to fill out patient diaries in the first 6 days after follow-up visit at trial day 2.

At each treatment day, patients receive 1) IPL of their whole face, 2) brimonidine is thereafter applied to the facial side randomized to treatment followed by 3) air-cooling, which is applied to the whole face of the patient in accordance with clinical guidelines.

Efficacy endpoints \& evaluation methods

Primary efficacy endpoint:

To investigate whether topical brimonidine can reduce IPL-induced inflammatory response

Secondary efficacy endpoints:

1. IPL-induced treatment efficacy on telangiectasias with and without application of brimonidine
2. Patient-evaluated subjective discomfort and pain in the treatment area
3. Overall patient satisfaction

Primary efficacy endpoint is quantified by reduction in erythema and oedema assessed by blinded clinical on-site evaluation and by blinded photo-evaluation.

Secondary efficacy endpoints regarding point 1 are quantified by blinded photo-evaluation obtained with a Visia camera, in which baseline-photos are compared to photos from the final follow-up visit. Point 2 and 3 are evaluated on two separate 0-10 point Visual Analogue Scales (VAS) on discomfort/pain and patient satisfaction, respectively. Patient satisfaction is further evaluated in patient diaries.

Product Mirvaso® (brimonidine tartrate (3,3mg/1g), Galderma Nordic) One gram of gel contains 3.3 mg of brimonidine, equivalent to 5 mg of brimonidine tartrate.

Excipient(s) with known effect:

One gram of gel contains 1 mg methylparahydroxybenzoate (E218) and 55 mg propylene glycol.

Other excipients:

* Carbomer Methylparahydroxybenzoate (E218) Phenoxyethanol
* Glycerol
* Titanium dioxide
* Propylene glycol
* Sodium hydroxide
* Purified water

Statistic analysis Primary efficacy endpoint is difference in inflammation between brimonidine vs. control.

Wilcoxon signed-rank test will be used for paired comparison to evaluate eventual differences between brimonidine vs. control. Analysis on Per-Protocol will only include the patients completing the study according to protocol.

Sample size Estimation of sample size is based on clinical on-site evaluation on inflammation 30 minutes after incubation of brimonidine (effect of brimonidine is evident after 30 minutes cf.´Summary of Product Characteristics) and 24 hours after application.

With a power of 90%, a type I error probability of 5% and an estimated standard deviation of 25%, we should include 17 patients to detect a minimum relevant difference (MIREDIF) of 20% between brimonidine and control. We choose a 20% MIREDIF, since a reduction in inflammation \<20%, based on a resource economic point of view is considered clinical irrelevant. Based on earlier experience and duration of the trial, a 15% dropout rate should be taken into account and therefore, a total of 20 patients will be included.

Eligibility criteria: Inclusion Criteria:

* Patients with moderate to severe facial telangiectasias referred to laser or IPL-treatment. Severity and distribution of telangiectasias must be symmetrical between left and right side of the face in the individual patient
* Telangiectasias may be observed in connection with rosacea, but rosacea must not demonstrate clinical active inflammation or acne
* 18-65 years of age
* Fitzpatrick skin type I-III
* Fertile women must document non-reactive urine pregnancy test at the day of inclusion
* During the study, fertile women must be using effective birth control. Effective contraception is defined as follows:

  * Injectable, implantable or orally taken hormones;
  * Intrauterine device;
  * Trans-abdominal surgical sterilization;
  * Sterilization implant device;
  * Surgical sterilization of male partner;
  * Complete abstinence from sexual intercourse for two weeks before exposure to study medication and throughout the clinical study
* Verbal and written consent to participate in the study
* Documentation of medicine status

Exclusion Criteria:

* Clinical active dermatological disease in the face
* Wounds, dermatitis, tattoos or scars in treatment area
* Allergies to ingredients in Mirvaso
* Current treatment with monoamine oxidase inhibitors, tricyclic or tetracyclic antidepressants which interacts with the noradrenergic transmission
* Current treatment with other systemic adrenergic receptor agonists or antagonists
* Patients with known liver or renal disease
* UV-exposure (solarium or sunbathing) or other treatment within the last month that enhances skin pigmentation
* Use of other topical agents that may interact with treatment
* Local or systemic treatment with photosensitizing drugs
* Pregnancy and breastfeeding women
* Current participation in other clinical trials
* Patients that are considered incapable of complying with the protocol, i.e. patients suffering from dementia, alcoholism or psychiatric conditions

Primary outcomes:
measure: Reduction in erythema quantified by blinded clinical on-site evaluation and by blinded photo-evaluation.
timeFrame: Throughout the study, a period of 10 weeks
measure: Reduction in oedema quantified by blinded clinical on-site evaluation and by blinded photo-evaluation.
timeFrame: Throughout the study, a period of 10 weeks
Secondary outcomes:
measure: The effect of brimonidine on IPL-efficacy quantified by blinded photo-evaluation obtained with a Visia camera, in which baseline-photos are compared to photos from the final follow-up visit.
timeFrame: At the end of the study (after 10 weeks)
measure: Patient discomfort and pain
timeFrame: Throughout the study, a period of 10 weeks
measure: Patient overall satisfaction
timeFrame: Throughout the study, a period of 10 weeks
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Bispebjerg Hospital
Study officials:
affiliation: Department of Dermatology
name: Merete Hædersdal, Prof., MD
role: PRINCIPAL_INVESTIGATOR
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