Brimonidine 0.33% for Rosacea-Related Facial Erythema

Acute and Short-Term Efficacy of 0.33% Brimonidine in Persistent Erythema of Rosacea: A Prospective Two-Phase Study Incorporating a Split-Face, Randomized, Placebo-Controlled Design and Objective Biophysical and Dermoscopic Assessments

This study looks at whether a topical gel called 0.33% brimonidine can reduce persistent facial redness caused by rosacea. The study was carried out in two parts.

In the first part, the gel was applied to only one side of each participant's face, while the other side received a placebo (a non-active gel). Redness was measured before and after application to see the immediate (short-term) effect.

In the second part, participants used brimonidine gel on both sides of the face once daily for one month. Redness and visible blood vessel changes were checked again at the end of this period.

Redness was evaluated using objective measurements of skin color, dermoscopic (magnified) images of facial blood vessels, and patient-reported symptoms such as burning or stinging.

The purpose of this study is to understand both the short-term and one-month effects of 0.33% brimonidine gel on persistent facial redness in people with rosacea.

Study Overview

• Status: Completed
• Conditions: Rosacea; Rosacea Subtype 1 (Erythematotelangiectatic)
• Intervention / Treatment: Drug: Brimonidine 0.33% gel; Drug: Placebo gel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul Training and Research Hospital, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Brimonidine 0.33% Gel; Facial half randomized to receive topical brimonidine tartrate 0.33% gel during the acute split-face phase.	Drug: Brimonidine 0.33% gel; 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 Comparator: Placebo Comparator: Vehicle Gel; Contralateral facial half randomized to receive vehicle gel during the acute split-face phase.	Drug: Placebo gel; Vehicle gel identical in appearance and texture to the active formulation, applied to the contralateral facial half during the acute split-face phase only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Erythema Index (EI) measured with Mexameter (MX18)	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.	Baseline (0 hour), 1 hour, and 3 hours on Day 1; and 0 hour and 1 hour at the 1-month visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dermoscopy Erythema Intensity Score (DEYS)	Semi-quantitative dermoscopic score evaluating erythema intensity on a predefined 0-4 scale. Higher scores indicate greater erythema intensity.	Day 1: 0 hour and 1 hour; and Month 1: 0 hour and 1 hour
Clinical Erythema Score (0-4 Scale)	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.	Day 1: 0 hour, 1 hour, and 3 hours; and Month 1: 0 hour and 1 hour
Patient Self-Assessment of Facial Redness (0-4 Scale)	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.	Day 1: 0 hour, 1 hour, and 3 hours; and Month 1: 0 hour and 1 hour
Hospital Anxiety and Depression Scale (HADS) Total Psychological Impact	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.	Baseline and Month 1
Skindex-16 Dermatology Quality of Life Score	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.	Baseline and Month 1
Dermoscopy Vessel Density Area Score (DDYAS)	Semi-quantitative dermoscopic score assessing vascular density in the evaluated facial region. Higher scores indicate greater vessel density.	Day 1 (0 hour, 1 hour); Month 1 (0 hour, 1 hour)
Average Vessel Thickness Score (ODKS)	Semi-quantitative dermoscopic score assessing average vessel thickness. Higher scores indicate thicker vessels.	Day 1 (0 hour, 1 hour); Month 1 (0 hour, 1 hour)

Collaborators and Investigators

• Sponsor: Istanbul Training and Research Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Actual): August 7, 2025
• Study Completion (Actual): August 7, 2025

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Rosacea; Patient-Reported Outcomes; Brimonidine; Dermoscopy; Prospective Study; Randomized Controlled; Telangiectasia; ETR; Hospital Anxiety and Depression Scale (HADS); Erythema Index; Mexameter; Persistent Erythema; Brimonidine 0.33% Gel; Topical Vasoconstrictor; Split-Face Study; Vascular Density; Skindex-16; Paradoxical Erythema; Rebound Erythema; Erythematotelangiectatic Rosacea; Rosacea Subtype I
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Behavioral Symptoms; Skin Diseases; Behavior; Skin and Connective Tissue Diseases; Depression; Telangiectasis; Rosacea; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Dosage Forms; Complex Mixtures; Colloids; Quinoxalines; Brimonidine Tartrate; Gels
• Other Study ID Numbers: SBU-IEAH-DER-BRIM-ROS-01; Medipol-EC-502 (Other Identifier: Istanbul Medipol University Non-Interventional Clinical Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No