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| Name | Class |
|---|---|
| Society for Pediatric Dermatology | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Timolol 0.5% Gel Forming Solution (GFS) | Experimental | Half of enrolled subjects will receive topical Timolol |
|
| Mupirocin 2% ointment | Active Comparator | Half of enrolled subjects will receive Mupirocin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Timolol 0.5% Gel Forming Solution (GFS) | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Wound Re-epithelization | At 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in Ulcer Surface Area and Depth | At 3 months | |
| Investigator's Global Evaluation of Disease | A scoring system developed to measure clinical improvement of ulcerated hemangioma. | At 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Albert C. Yan, MD | Children's Hospital of Philadelphia, Chair of Pediatric Dermatology | Principal Investigator |
| Vikash S. Oza, MD | Children's Hospital of Philadelphia, Attending Physician | Principal Investigator |
| Patrick McMahon, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20479314 | Background | 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. | |
| 19143471 | Background | 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. |
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| ID | Term |
|---|---|
| D006391 | Hemangioma |
| D018324 | Hemangioma, Capillary |
| D054079 | Vascular Malformations |
| ID | Term |
|---|---|
| D009383 | Neoplasms, Vascular Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018376 | Cardiovascular Abnormalities |
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| ID | Term |
|---|---|
| D013999 | Timolol |
| D016712 | Mupirocin |
| D009824 | Ointments |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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|
|
| Mupirocin 2% Ointment | Drug | Topical application twice per day for 60 days |
|
|
| Timolol Serum Level | Measured at 1 month into therapy |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 19706583 | Background | 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. |
| 21158749 | Background | 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. |
| 18035154 | Background | 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. |
| D002318 | Cardiovascular Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020005 |
| Propanols |
| D000588 | Amines |
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009025 | Morpholines |
| D010078 | Oxazines |
| D004852 | Epoxy Compounds |
| D004988 | Ethers, Cyclic |
| D004987 | Ethers |
| D011714 | Pyrans |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |