Timolol Option for Ulcerated Hemangiomas (TOUCH Trial)

This study has been withdrawn prior to enrollment.
(Difficulty with recruitment)
Sponsor:
Collaborator:
Society for Pediatric Dermatology
Information provided by (Responsible Party):
Albert Yan, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01408056
First received: March 10, 2011
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Infantile Hemangiomas
Drug: Timolol 0.5% Gel Forming Solution (GFS)
Drug: Mupirocin 2% Ointment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Efficacy of Timolol 0.5% Gel Forming Solution for the Treatment of Ulcerated Hemangiomas

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Time to Wound Re-epithelization [ Time Frame: At 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction in Ulcer Surface Area and Depth [ Time Frame: At 3 months ] [ Designated as safety issue: No ]
  • Investigator's Global Evaluation of Disease [ Time Frame: At 3 months ] [ Designated as safety issue: No ]
    A scoring system developed to measure clinical improvement of ulcerated hemangioma.

  • Timolol Serum Level [ Time Frame: Measured at 1 month into therapy ] [ Designated as safety issue: Yes ]
  • Evaluate number of participants with changes in Glucose levels after drug is applied [ Time Frame: Baseline, day 7, day 14 ] [ Designated as safety issue: Yes ]

    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.


  • Evaluate number of participants with evidence of changes in blood pressure following administration of Timolol 0.5% GFS [ Time Frame: Baseline, day 7, day 14 ] [ Designated as safety issue: Yes ]

    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.


  • Pain scores (presence or absence) on the Wong-Baker faces scale [ Time Frame: Baseline, day 7, day 14, 1 month, 2 months ] [ Designated as safety issue: Yes ]

    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.


  • Number of participants with presence or absence of Infection [ Time Frame: Baseline, day 7, day 14, 1 month, 2 months ] [ Designated as safety issue: Yes ]

    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.


  • Number of participants with presence (or absence) of active bleeding [ Time Frame: Baseline, day 7, day 14, 1 month, 2 months ] [ Designated as safety issue: Yes ]

    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.


  • Evaluate number of participants with changes in Heart Rate after drug is applied [ Time Frame: Baseline, day 7, day 14 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 0
Study Start Date: February 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Timolol 0.5% Gel Forming Solution (GFS)
Half of enrolled subjects will receive topical Timolol
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

Other Name: Timolol 0.5% topical
Active Comparator: Mupirocin 2% ointment
Half of enrolled subjects will receive Mupirocin
Drug: Mupirocin 2% Ointment
Topical application twice per day for 60 days
Other Name: Mupirocin

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

Ages Eligible for Study:   1 Month to 8 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408056

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Society for Pediatric Dermatology
Investigators
Principal Investigator: 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
  More Information

Publications:
Responsible Party: Albert Yan, Chief, Section of Pediatric Dermatology, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01408056     History of Changes
Other Study ID Numbers: 10-007923
Study First Received: March 10, 2011
Last Updated: January 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Hemangioma
Infantile Hemangioma
Ulcerated Hemangioma
Timolol
Beta blocker
Vascular anomaly

Additional relevant MeSH terms:
Hemangioma
Hemangioma, Capillary
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Pharmaceutical Solutions
Timolol
Mupirocin
Therapeutic Uses
Pharmacologic Actions
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014