Topical Brimonidine to Reduce Inflammation After IPL-treatment in Patients With Facial Telangiectasias
Topical Brimonidine to Reduce Inflammation After IPL-treatment in Patients With Facial Telangiectasias
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.
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.
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