Topical Brimonidine to Reduce Inflammation After IPL-treatment in Patients With Facial Telangiectasias
Condition: Telangiectasias
MeSH terms: Telangiectasis
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Brimonidine; IPL+air-cooling
Intervention type(s): Drug; Other
Intervention description(s): Patients receive brimonidine to half of their face, whereas the other half receives no treatment and thereby patients are their own control; IPL+air-cooling are applied to the whole face and the control side thereby only receives IPL+air-cooling
Other intervention name(s): Mirvaso cream
Intervention MeSH terms: Brimonidine Tartrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vascular lesions; inflammation; IPL