Brimonidine 0.33% for Rosacea-Related Facial Erythema

This prospective, two-phase clinical study was designed to evaluate the acute and short-term effects of 0.33% brimonidine gel on persistent facial erythema associated with rosacea. The study included an acute phase using a split-face, randomized, placebo-controlled methodology, followed by a one-month open-label phase.

In the acute phase, each participant received brimonidine gel on one half of the face and a placebo gel on the opposite side. The assignment of treatment sides was randomized for each participant. Erythema measurements were obtained at baseline (0 hour) and again one hour after application to assess the immediate vasoconstrictive effect of brimonidine. Dermoscopic imaging was performed to evaluate vascular morphology, including erythema intensity, vascular density, vessel caliber, and the area of involvement. These dermoscopic parameters were scored using predefined semi-quantitative scales developed for this study.

In the second phase, all participants applied 0.33% brimonidine gel once daily to the entire face for one month. At the end of the one-month period, erythema measurements and dermoscopic evaluations were repeated before and one hour after application to determine whether the acute response to brimonidine changed with continuous daily use. Patient-reported outcomes, including burning, stinging, and other treatment-related symptoms, were also recorded during both phases.

Objective erythema was quantified using a biophysical measurement device (erythema index), which provided standardized and reproducible assessments of skin redness. The use of both biophysical measurements and dermoscopic visualization allowed for a comprehensive evaluation of the drug's clinical and vascular effects.

No investigational new drug application (IND) was involved, and the product used was a commercially available formulation of brimonidine. All study procedures were performed under ethics committee approval, and written informed consent was obtained from all participants.

• Brimonidine 0.33% gel (Drug): Topical brimonidine tartrate 0.33% gel applied to one randomized facial half during the acute split-face phase. After completion of the acute assessment, all participants enter a 1-month open-label phase with once-daily full-face application.
• Placebo gel (Drug): Vehicle gel identical in appearance and texture to the active formulation, applied to the contralateral facial half during the acute split-face phase only.

Primary outcomes

• Change in Erythema Index (EI) measured with Mexameter (MX18) [Baseline (0 hour), 1 hour, and 3 hours on Day 1; and 0 hour and 1 hour at the 1-month visit]: The primary outcome is the change in objective erythema values measured using the Mexameter (MX18) device. Acute effects will be assessed by comparing EI measurements at baseline (0 hour), 1 hour, and 3 hours after the single split-face application of brimonidine versus placebo on Day 1. Short-term effects will be assessed at the 1-month visit by comparing EI values at 0 hour and 1 hour following 1 month of daily home use of brimonidine. Higher EI values indicate greater erythema.

Secondary outcomes

• Dermoscopy Erythema Intensity Score (DEYS) [Day 1: 0 hour and 1 hour; and Month 1: 0 hour and 1 hour]: Semi-quantitative dermoscopic score evaluating erythema intensity on a predefined 0-4 scale. Higher scores indicate greater erythema intensity.
• Clinical Erythema Score (0-4 Scale) [Day 1: 0 hour, 1 hour, and 3 hours; and Month 1: 0 hour and 1 hour]: The Clinical Erythema Score (CES) is a semi-quantitative 0-4 scale used to assess the severity of visible facial erythema. A score of 0 indicates no erythema, 1 mild erythema, 2 moderate erythema, 3 marked erythema, and 4 severe/intense erythema. Assessments are performed at Day 1 (0 hour, 1 hour, and 3 hours after the split-face application) and at the 1-month visit (0 hour and 1 hour) following daily home use of brimonidine. Higher scores indicate more pronounced clinical erythema.
• Patient Self-Assessment of Facial Redness (0-4 Scale) [Day 1: 0 hour, 1 hour, and 3 hours; and Month 1: 0 hour and 1 hour]: Participants rate the severity of their facial redness using a 0-4 self-assessment scale. A score of 0 indicates no redness, 1 mild redness, 2 moderate redness, 3 marked redness, and 4 severe/intense redness. Assessments are performed at Day 1 (0 hour, 1 hour, and 3 hours after split-face application) and at the 1-month visit (0 hour and 1 hour) following daily home use of brimonidine. Higher scores indicate greater patient-perceived redness.
• Hospital Anxiety and Depression Scale (HADS) Total Psychological Impact [Baseline and Month 1]: The psychological impact of rosacea-related facial erythema is assessed using the Hospital Anxiety and Depression Scale (HADS), which includes two subscores: Anxiety (HADS-A) and Depression (HADS-D). Each subscale ranges from 0 to 21, with higher scores indicating more severe symptoms. The scale is administered at baseline and at the 1-month visit to evaluate whether changes in erythema severity are associated with changes in anxiety or depressive symptoms.
• Skindex-16 Dermatology Quality of Life Score [Baseline and Month 1]: Dermatology-specific quality of life is assessed using the Skindex-16 questionnaire, which includes three domains: Symptoms, Emotions, and Functioning. Each item is scored from 0 to 6, with higher scores indicating greater impairment. Total and domain scores are recorded at baseline and at the 1-month visit to evaluate changes in quality of life related to improvements in facial erythema.
• Dermoscopy Vessel Density Area Score (DDYAS) [Day 1 (0 hour, 1 hour); Month 1 (0 hour, 1 hour)]: Semi-quantitative dermoscopic score assessing vascular density in the evaluated facial region. Higher scores indicate greater vessel density.
• Average Vessel Thickness Score (ODKS) [Day 1 (0 hour, 1 hour); Month 1 (0 hour, 1 hour)]: Semi-quantitative dermoscopic score assessing average vessel thickness. Higher scores indicate thicker vessels.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adults aged 18 years or older
* Clinical diagnosis of erythematotelangiectatic rosacea (ETR) according to the National Rosacea Society (NRS) diagnostic criteria
* Presence of persistent facial erythema consistent with ETR
* Symmetrical facial involvement adequate for split-face assessment
* No more than two inflammatory facial lesions at screening
* Ability and willingness to comply with all study procedures, including acute Day 1 assessments and the 1-month follow-up visit
* Willingness to apply topical brimonidine gel daily during the 1-month period and to avoid initiating new rosacea treatments during the study
* Provision of written informed consent

Exclusion Criteria:

* Individuals younger than 18 years.
* Presence of three or more inflammatory facial lesions.
* Prior use of BT (brimonidine tartrate) for facial erythema.
* Use of topical or systemic treatments for rosacea or other dermatoses without completing the required washout period.
* Presence of other facial dermatoses
* Withdrawal of consent (the only discontinuation criterion)

• Results publication: Fowler J Jr, Jackson M, Moore A, Jarratt M, Jones T, Meadows K, Steinhoff M, Rudisill D, Leoni M. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies. J Drugs Dermatol. 2013 Jun 1;12(6):650-6. PMID 23839181