Clinical trial NCT01408056: Timolol Option for Ulcerated Hemangiomas (TOUCH Trial)
Official title: The Efficacy of Timolol 0.5% Gel Forming Solution for the Treatment of Ulcerated Hemangiomas
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Infantile Hemangiomas
Keywords: Hemangioma
Infantile Hemangioma
Ulcerated Hemangioma
Timolol
Beta blocker
Vascular anomaly
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Society for Pediatric Dermatology
First posted: 2011-08-03
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Timolol 0.5% Gel Forming Solution is safe and effective in promoting wound healing of infantile ulcerated hemangiomas compared with standard conservative management with topical antibiotic.

Detailed description: Ulceration is the most common complication associated with infantile hemangiomas. Ulceration and the delay in wound healing places patients at risk for infection, bleeding, pain and permanent scarring. Currently, the care of ulcerated hemangiomas is extremely difficult and patients are often subject to multiple treatment modalities.

In the past two years, the leading advance in the treatment of hemangiomas has been the use of the non-selective, oral beta-blocker propranolol to arrest growth and promote involution of hemangiomas. Recent literature also suggests beta-blockers may have a role in helping ulcerated wounds re-epithelialize.

The use of a topical non-selective beta-blocker on isolated ulcerated hemangiomas may promote early healing and reduce the number of complications associated with ulceration. Investigation is needed to explore the safety and tolerability of applying a topical beta-blocker on an ulcerated hemangioma and whether topical beta-blockade may be more efficacious than conservative care with topical antibiotics.

In this study, infants will be randomized to either receive a topical antibiotic (topical mupirocin 2% ointment twice per day) or a topical beta-blocker (Timolol 0.5% Gel Forming Solution) according to a dose-escalation schedule. Subjects will be seen in clinic on day 7, day 14, 1 month and 2 months into therapy and 1 month after therapy is completed. Photographs and safety and efficacy measurements will be taken at each visit to assess response to therapy.

Eligibility criteria: Inclusion Criteria:

* Infants weighing between 4-12kg
* Infants with corrected gestational age 44 weeks - 8 months of age
* Infant with an ulcerated hemangioma
* Informed consent

Exclusion Criteria:

* Ulceration larger than 16cm2
* Ulcerated hemangioma with active bleeding or infection at time of enrollment
* Disease threatening hemangioma meeting criteria for oral propranolol
* Previous treatment with topical/oral corticosteroid or propranolol
* Medical history of congenital heart disease with decreased cardiac output, stroke/cerebral vasculopathy, active reactive airway disease or metabolic disorder
* History of an allergic reaction to Mupirocin or Timolol
* Currently taking medication that would interact with beta-blockers

Primary outcomes:
measure: Time to Wound Re-epithelization
timeFrame: At 3 months
Secondary outcomes:
measure: Reduction in Ulcer Surface Area and Depth
timeFrame: At 3 months
measure: Investigator's Global Evaluation of Disease
timeFrame: At 3 months
measure: Timolol Serum Level
timeFrame: Measured at 1 month into therapy
measure: Evaluate number of participants with changes in Glucose levels after drug is applied
timeFrame: Baseline, day 7, day 14
measure: Evaluate number of participants with evidence of changes in blood pressure following administration of Timolol 0.5% GFS
timeFrame: Baseline, day 7, day 14
measure: Pain scores (presence or absence) on the Wong-Baker faces scale
timeFrame: Baseline, day 7, day 14, 1 month, 2 months
measure: Number of participants with presence or absence of Infection
timeFrame: Baseline, day 7, day 14, 1 month, 2 months
measure: Number of participants with presence (or absence) of active bleeding
timeFrame: Baseline, day 7, day 14, 1 month, 2 months
measure: Evaluate number of participants with changes in Heart Rate after drug is applied
timeFrame: Baseline, day 7, day 14
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia, Chair of Pediatric Dermatology
name: Albert C. Yan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia, Attending Physician
name: Vikash S. Oza, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Patrick McMahon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a pilot study. Arch Dermatol. 2010 May;146(5):564-5. doi: 10.1001/archdermatol.2010.67. No abstract available.
citation: Sivamani RK, Pullar CE, Manabat-Hidalgo CG, Rocke DM, Carlsen RC, Greenhalgh DG, Isseroff RR. Stress-mediated increases in systemic and local epinephrine impair skin wound healing: potential new indication for beta blockers. PLoS Med. 2009 Jan 13;6(1):e12. doi: 10.1371/journal.pmed.1000012.
citation: Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, Lipsker D, Dupuis E, Ezzedine K, Vergnes P, Taieb A, Leaute-Labreze C. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics. 2009 Sep;124(3):e423-31. doi: 10.1542/peds.2008-3458. Epub 2009 Aug 10.
citation: Khunger N, Pahwa M. Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome. Br J Dermatol. 2011 Apr;164(4):886-8. doi: 10.1111/j.1365-2133.2010.10177.x. No abstract available.
citation: Chamlin SL, Haggstrom AN, Drolet BA, Baselga E, Frieden IJ, Garzon MC, Horii KA, Lucky AW, Metry DW, Newell B, Nopper AJ, Mancini AJ. Multicenter prospective study of ulcerated hemangiomas. J Pediatr. 2007 Dec;151(6):684-9, 689.e1. doi: 10.1016/j.jpeds.2007.04.055. Epub 2007 Aug 24.