Timolol Option for Ulcerated Hemangiomas (TOUCH Trial)

Condition(s) targeted: Infantile Hemangiomas

Intervention: Timolol 0.5% Gel Forming Solution (GFS) (Drug); Mupirocin 2% Ointment (Drug)

Phase: Phase 2

Status: Withdrawn

Sponsored by: Children's Hospital of Philadelphia

Official(s) and/or principal investigator(s):
Albert C. Yan, MD, Principal Investigator, Affiliation: Children's Hospital of Philadelphia, Chair of Pediatric Dermatology
Vikash S. Oza, MD, Principal Investigator, Affiliation: Children's Hospital of Philadelphia, Attending Physician
Patrick McMahon, MD, Principal Investigator, Affiliation: Children's Hospital of Philadelphia

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.

Official title: The Efficacy of Timolol 0.5% Gel Forming Solution for the Treatment of Ulcerated Hemangiomas

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Time to Wound Re-epithelization

Secondary outcome:

Reduction in Ulcer Surface Area and Depth

Investigator's Global Evaluation of Disease

Timolol Serum Level

Evaluate number of participants with changes in Glucose levels after drug is applied

Evaluate number of participants with evidence of changes in blood pressure following administration of Timolol 0.5% GFS

Pain scores (presence or absence) on the Wong-Baker faces scale

Number of participants with presence or absence of Infection

Number of participants with presence (or absence) of active bleeding

Evaluate number of participants with changes in Heart Rate after drug is applied

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.

Minimum age: 1 Month. Maximum age: 8 Months. Gender(s): Both.

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

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Related publications:

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.

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.

Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, Lipsker D, Dupuis E, Ezzedine K, Vergnes P, Taïeb A, Léauté-Labrèze 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.

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.

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. Epub 2007 Aug 24. Erratum in: J Pediatr. 2008 Apr;152(4):597.

Starting date: February 2011
Last updated: January 16, 2014