Timolol Option for Ulcerated Hemangiomas (TOUCH Trial)

Infantile Hemangiomas Clinical Trial

— TOUCH  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01408056
• Other study ID #: 10-007923
• Status: Withdrawn
• Phase: Phase 2
• First received: March 10, 2011
• Last updated: January 16, 2014
• Start date: February 2011
• Est. completion date: January 2014

Study information

• Verified date: January 2014
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 8 Months

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Hemangioma
• Hemangioma, Capillary
• Infantile Hemangiomas
• Port-Wine Stain

Intervention

Drug:
• Timolol 0.5% Gel Forming Solution (GFS)
Dose-based escalation schedule for topical application: 4-8 kg: Day 0-7: 1 drop every other day; Day 7-14: 1 drop daily; Day 14 - Day 60: 1 drop twice per day 8-12 kg: Day 07: 1 drop daily; Day 7-14: 1 drop twice per day; Day 14 - Day 60: 2 drops twice per day
• Mupirocin 2% Ointment
Topical application twice per day for 60 days

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Society for Pediatric Dermatology

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View Citation

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Wound Re-epithelization		At 3 months	No
Secondary	Reduction in Ulcer Surface Area and Depth		At 3 months	No
Secondary	Investigator's Global Evaluation of Disease	A scoring system developed to measure clinical improvement of ulcerated hemangioma.	At 3 months	No
Secondary	Timolol Serum Level		Measured at 1 month into therapy	Yes
Secondary	Evaluate number of participants with changes in Glucose levels after drug is applied	Glucose monitoring will be performed for patients receiving Timolol 0.5% GFS before and 1 hour after drug is applied in clinic.; Glucose values < 60 mg/dL will be considered significant.; 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.	Baseline, day 7, day 14	Yes
Secondary	Evaluate number of participants with evidence of changes in blood pressure following administration of Timolol 0.5% GFS	Blood pressure monitoring will be performed for patients receiving Timolol 0.5% GFS before and 1 hour after drug is applied in clinic.; Blood pressure values < 3rd percentile (systolic or diastolic) will be considered significant for hypotension.; 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.	Baseline, day 7, day 14	Yes
Secondary	Pain scores (presence or absence) on the Wong-Baker faces scale	Investigators will question caregivers about common complications of ulcerated hemangiomas (pain, infection, bleeding) at each visit throughout the study. Pain will be assessed using the Wong-Baker faces scale.; 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.	Baseline, day 7, day 14, 1 month, 2 months	Yes
Secondary	Number of participants with presence or absence of Infection	Investigators will question caregivers about common complications of ulcerated hemangiomas (pain, infection, bleeding) at each visit throughout the study. Infection will be clinically assessed by presence of drainage or exudate, and/or culture positivity.; 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.	Baseline, day 7, day 14, 1 month, 2 months	Yes
Secondary	Number of participants with presence (or absence) of active bleeding	Investigators will question caregivers about common complications of ulcerated hemangiomas (pain, infection, bleeding) at each visit throughout the study. Infection will be clinically assessed by presence of active bleeding.; 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.	Baseline, day 7, day 14, 1 month, 2 months	Yes
Secondary	Evaluate number of participants with changes in Heart Rate after drug is applied	Glucose and vital sign monitoring will be performed for patients receiving Timolol 0.5% GFS before and 1 hour after drug is applied in clinic.; Heart rate values < 3rd percentile will be considered significant and indicative of bradycardia.; 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.	Baseline, day 7, day 14	Yes