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

• ClinicalTrials.gov Identifier: NCT02761174
• Recruitment Status: Completed
• First Posted: May 4, 2016
• Last Update Posted: January 5, 2018
• Sponsor: Merete Haedersdal
• Collaborators: Skinperium, Christine Dierickx; Ellipse A/S Agern Allé 11, 2970 Hørsholm
• Information provided by (Responsible Party): Merete Haedersdal, Bispebjerg Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Telangiectasias	Drug: Brimonidine; Other: IPL+air-cooling	Phase 4

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Topical Brimonidine Reduces IPL-induced Erythema Without Affecting Efficacy: a Randomized Controlled Trial in Patients With Facial Telangiectasias
• Actual Study Start Date: March 13, 2016
• Actual Primary Completion Date: July 11, 2016
• Actual Study Completion Date: January 13, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Brimonidine (Mirvaso cream); This is a split-face study, and patients are thereby their own control. Patients receive IPL-treatment and air-cooling to the whole face (control) and 0.5 g of brimonidine (Mirvaso cream) to the randomized side of the face.	Drug: Brimonidine; Patients receive brimonidine to half of their face, whereas the other half receives no treatment and thereby patients are their own control; Other Name: Mirvaso cream
IPL+air-cooling; This is a split-face study, and patients are thereby their own control. Patients receive IPL-treatment and air-cooling to the whole face and IPL+air-cooling (control) are thereby compared to IPL+air-cooling+brimonidine (Mirvaso cream).	Other: IPL+air-cooling; IPL+air-cooling are applied to the whole face and the control side thereby only receives IPL+air-cooling

Outcome Measures

Primary Outcome Measures :

1. Reduction in erythema quantified by blinded clinical on-site evaluation and by blinded photo-evaluation. [ Time Frame: Throughout the study, a period of 10 weeks ]

   Erythema is evaluated on the international validated, "Clinician's Erythema Assessment" (CEA) 5-point scale:

   0, Clear Clear skin with no signs of erythema

   1. Almost clear Almost clear; slight redness
   2. Mild Mild erythema; definite redness
   3. Moderate Moderate erythema; marked redness
   4. Severe Severe erythema; fiery redness
2. Reduction in oedema quantified by blinded clinical on-site evaluation and by blinded photo-evaluation. [ Time Frame: Throughout the study, a period of 10 weeks ]
   Oedema is evaluated on a 4-point scale: 0 = no oedema, 1 = little oedema, 2 = moderate oedema and 3 = severe oedema.

Secondary Outcome Measures :

1. 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. [ Time Frame: At the end of the study (after 10 weeks) ]
   Baseline photos are compared to photos at final follow-up visit approximate 10 weeks after.
2. Patient discomfort and pain [ Time Frame: Throughout the study, a period of 10 weeks ]
   Patient discomfort and pain are evaluated on a numeric Visual Analogue Scale (VAS) from 0 (no discomfort/pain) to 10 (extreme discomfort/pain) separately for brimonidine and control
3. Patient overall satisfaction [ Time Frame: Throughout the study, a period of 10 weeks ]
   Patients evaluate their overall satisfaction with brimonidine to reduce IPL-induced inflammation on a numeric VAS from 0 (poor outcome) to 10 (excellent outcome). Inflammation is described as redness, swelling and pain to the patient.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Denmark

Bispebjerg Hospital

Copenhagen NV, Denmark, 2200

Sponsors and Collaborators

Merete Haedersdal

Skinperium, Christine Dierickx

Ellipse A/S Agern Allé 11, 2970 Hørsholm

Investigators

• Principal Investigator: Merete Hædersdal, Prof., MD; Department of Dermatology

More Information

Additional Information:

European Medicines Agency 

Publications:

Tierney E, Hanke CW. Randomized controlled trial: Comparative efficacy for the treatment of facial telangiectasias with 532 nm versus 940 nm diode laser. Lasers Surg Med. 2009 Oct;41(8):555-62. doi: 10.1002/lsm.20811.

Adamič M, Pavlović MD, Troilius Rubin A, Palmetun-Ekbäck M, Boixeda P. Guidelines of care for vascular lasers and intense pulse light sources from the European Society for Laser Dermatology. J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1661-78. doi: 10.1111/jdv.13177. Epub 2015 Apr 30.

Taub AF, Devita EC. Successful treatment of erythematotelangiectatic rosacea with pulsed light and radiofrequency. J Clin Aesthet Dermatol. 2008 May;1(1):37-40.

Tanghetti EA. Split-face randomized treatment of facial telangiectasia comparing pulsed dye laser and an intense pulsed light handpiece. Lasers Surg Med. 2012 Feb;44(2):97-102. doi: 10.1002/lsm.21151. Epub 2011 Dec 16.

Nymann P, Hedelund L, Haedersdal M. Long-pulsed dye laser vs. intense pulsed light for the treatment of facial telangiectasias: a randomized controlled trial. J Eur Acad Dermatol Venereol. 2010 Feb;24(2):143-6.

Uebelhoer NS, Bogle MA, Stewart B, Arndt KA, Dover JS. A split-face comparison study of pulsed 532-nm KTP laser and 595-nm pulsed dye laser in the treatment of facial telangiectasias and diffuse telangiectatic facial erythema. Dermatol Surg. 2007 Apr;33(4):441-8.

Papageorgiou P, Clayton W, Norwood S, Chopra S, Rustin M. Treatment of rosacea with intense pulsed light: significant improvement and long-lasting results. Br J Dermatol. 2008 Sep;159(3):628-32. doi: 10.1111/j.1365-2133.2008.08702.x. Epub 2008 Jun 28.

Clark C, Cameron H, Moseley H, Ferguson J, Ibbotson SH. Treatment of superficial cutaneous vascular lesions: experience with the KTP 532 nm laser. Lasers Med Sci. 2004;19(1):1-5. Epub 2004 Apr 14.

Eremia S, Li CY. Treatment of face veins with a cryogen spray variable pulse width 1064 nm Nd:YAG Laser: a prospective study of 17 patients. Dermatol Surg. 2002 Mar;28(3):244-7.

Bjerring P, Christiansen K, Troilius A. Intense pulsed light source for treatment of facial telangiectasias. J Cosmet Laser Ther. 2001 Dec;3(4):169-73.

Mark KA, Sparacio RM, Voigt A, Marenus K, Sarnoff DS. Objective and quantitative improvement of rosacea-associated erythema after intense pulsed light treatment. Dermatol Surg. 2003 Jun;29(6):600-4.

Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science. 1983 Apr 29;220(4596):524-7.

Srinivas CR, Kumaresan M. Lasers for vascular lesions: standard guidelines of care. Indian J Dermatol Venereol Leprol. 2011 May-Jun;77(3):349-68. doi: 10.4103/0378-6323.79728.

Handley JM. Adverse events associated with nonablative cutaneous visible and infrared laser treatment. J Am Acad Dermatol. 2006 Sep;55(3):482-9. Review.

Alam M, Omura NE, Dover JS, Arndt KA. Clinically significant facial edema after extensive treatment with purpura-free pulsed-dye laser. Dermatol Surg. 2003 Sep;29(9):920-4.

Lou WW, Quintana AT, Geronemus RG, Grossman MC. Effects of topical vitamin K and retinol on laser-induced purpura on nonlesional skin. Dermatol Surg. 1999 Dec;25(12):942-4.

Leu S, Havey J, White LE, Martin N, Yoo SS, Rademaker AW, Alam M. Accelerated resolution of laser-induced bruising with topical 20% arnica: a rater-blinded randomized controlled trial. Br J Dermatol. 2010 Sep;163(3):557-63. doi: 10.1111/j.1365-2133.2010.09813.x.

Alonso D, Lazarus MC, Baumann L. Effects of topical arnica gel on post-laser treatment bruises. Dermatol Surg. 2002 Aug;28(8):686-8.

Oge' LK, Muncie HL, Phillips-Savoy AR. Rosacea: Diagnosis and Treatment. Am Fam Physician. 2015 Aug 1;92(3):187-96.

Benkali K, Leoni M, Rony F, Bouer R, Fernando A, Graeber M, Wagner N. Comparative pharmacokinetics and bioavailability of brimonidine following ocular and dermal administration of brimonidine tartrate ophthalmic solution and gel in patients with moderate-to-severe facial erythema associated with rosacea. Br J Dermatol. 2014 Jul;171(1):162-9. doi: 10.1111/bjd.12881. Epub 2014 Jul 16.

Piwnica D, Rosignoli C, de Ménonville ST, Alvarez T, Schuppli Nollet M, Roye O, Jomard A, Aubert J. Vasoconstriction and anti-inflammatory properties of the selective α-adrenergic receptor agonist brimonidine. J Dermatol Sci. 2014 Jul;75(1):49-54. doi: 10.1016/j.jdermsci.2014.04.002. Epub 2014 Apr 16.

Fowler J, Jarratt M, Moore A, Meadows K, Pollack A, Steinhoff M, Liu Y, Leoni M; Brimonidine Phase II Study Group. Once-daily topical brimonidine tartrate gel 0·5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies. Br J Dermatol. 2012 Mar;166(3):633-41. doi: 10.1111/j.1365-2133.2011.10716.x.

Fowler J, Tan J, Jackson JM, Meadows K, Jones T, Jarratt M, Leoni M; Brimonidine Phase III Study Group. Treatment of facial erythema in patients with rosacea with topical brimonidine tartrate: correlation of patient satisfaction with standard clinical endpoints of improvement of facial erythema. J Eur Acad Dermatol Venereol. 2015 Mar;29(3):474-81. doi: 10.1111/jdv.12587. Epub 2014 Jul 30.

van Zuuren EJ, Fedorowicz Z. Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments. Br J Dermatol. 2015 Sep;173(3):651-62. doi: 10.1111/bjd.13956. Epub 2015 Aug 30. Review.

Johnson AW, Johnson SM. The Role of Topical Brimonidine Tartrate Gel as a Novel Therapeutic Option for Persistent Facial Erythema Associated with Rosacea. Dermatol Ther (Heidelb). 2015 Sep;5(3):171-81. doi: 10.1007/s13555-015-0078-1. Epub 2015 Jun 26.

Holmes AD, Waite KA, Chen MC, Palaniswamy K, Wiser TH, Draelos ZD, Rafal ES, Werschler WP, Harvey AE. Dermatological Adverse Events Associated with Topical Brimonidine Gel 0.33% in Subjects with Erythema of Rosacea: A Retrospective Review of Clinical Studies. J Clin Aesthet Dermatol. 2015 Aug;8(8):29-35. Review.

Moore A, Kempers S, Murakawa G, Weiss J, Tauscher A, Swinyer L, Liu H, Leoni M. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study. J Drugs Dermatol. 2014 Jan;13(1):56-61.

• Responsible Party: Merete Haedersdal, Professor, MD, DMSc, PhD, Bispebjerg Hospital
• ClinicalTrials.gov Identifier: NCT02761174 History of Changes
• Other Study ID Numbers: 2015-004789-27
• First Posted: May 4, 2016
• Last Update Posted: January 5, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Sponsor and investigator allow access to registries, CRF and trial master files in case of audit or quality inspection from relevant authorities such as GCP-unit, Danish Health and Medicine Authority or The Regional Committee on Health Research Ethics

Keywords provided by Merete Haedersdal, Bispebjerg Hospital:

Vascular lesions; inflammation; IPL

Additional relevant MeSH terms:

Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Brimonidine Tartrate; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs