Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial) (TiPPIH)

Tracking Information
First Submitted Date ICMJE	August 31, 2011
First Posted Date ICMJE	September 15, 2011
Last Update Posted Date	November 15, 2016
Study Start Date ICMJE	July 2012
Actual Primary Completion Date	April 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 22, 2011)	Proportion of subjects in treatment group compared to placebo group with at least 50% improvement in the extent of hemangioma as compared to each other with respect to changes from baseline photographs. [ Time Frame: 6 months ]; hemangioma once detected will be measured and photographed. Measurements and photographs will be obtained every 2 weeks while the patient is in hospital and monthly after discharged until end point of 6 months.
Original Primary Outcome Measures ICMJE; (submitted: September 14, 2011)	Proportion of subjects in treatment group compared to placebo group with at least 50% improvement in the extent of hemangioma as compared to baseline photographs. [ Time Frame: 6 months ]; hemangioma once detected will be measured and photographed. Measurements and photographs will be obtained every 2 weeks while the patient is in hospital and monthly after discharged until end point of 6 months.
Change History	Complete list of historical versions of study NCT01434849 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 14, 2011)	Compare treatment group to placebo group assessments [ Time Frame: 6 months ]Difference in color of the hemangioma of the treatment group versus control group; Compare treatment group to placebo group assessments [ Time Frame: 6 months ]More significant Retinopathy of Prematurity findings between treatment group versus control group; Compare treatment group to placebo group assessments [ Time Frame: 6 months ]Frequency of adverse events (e.g. hypotension, behavioral changes, etc.) collected by investigator and reported by NICU staff and parents.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial)
Official Title ICMJE	Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma
Brief Summary	The purpose of this trial is to see if a topical beta blocker is effective in preventing the proliferation of infantile hemangioma.
Detailed Description	Infantile hemangiomas (IH) are among the most common, benign vascular tumors of infancy with an estimated prevalence of 4-5% of the population. IH are not found at birth but become evident within the first few weeks of life. They are characterized by a rapid proliferative phase that can last up to 4-6 months or longer and then a period of minimal or absent growth before an involutive phase where they may resolve with minimal or no scarring over multiple years. Although frequently thought of as benign lesions, hemangiomas can occur in locations to cause functional impairment of vital organs, can lead to ulcerations, scarring or disfigurement, and can lead to life-threatening complications. Management of these problematic IH includes laser, long-term systemic corticosteroids, interferon, Vincristine, surgery, and most recently systemic propranolol. Pulsed-dye laser is the only treatment approved by the FDA; it has been useful for superficial hemangiomas but has little effect on subcutaneous or deep-seated hemangiomas. The proposed therapeutic effects of propranolol are vasoconstriction, decreased expression of vascular endothelial growth factor (VEGR) and basic fibroblast growth factors (bFGF) genes through downregulation of Raf/mitogen-activated protein kinase pathway, and apoptosis of capillary endothelial cells. For periorbital lesions that may cause amblyopia or anisometropia, topical Timolol has been reported to be of benefit. There is one retrospective review that is proof of concept that shows that topical timolol is safe and effective treatment for 6 cases of IH. The advantage of a topical therapy is the decreased risk of systemic side effects compared with oral or intravenous administration. The disadvantage is that limited penetration may preclude effectiveness for the thicker or deeper lesions. Being of low birth weight as well as prematurity are known risk factors for IH. In the premature infant development clinic at the University of Texas Health Science Center in San Antonio infants less than 1500 grams birth weight are followed for three years following discharge from the Newborn Intensive Care Unit (NICU); approximately 16% of these infants have hemangiomas. Therefore the investigators find it reasonable to start treatment with a topical beta blocker at an early stage of hemangioma to prevent the growth and proliferation and hence the possible severe effects associated with growth and thus impairment of vital organs/tissues.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition ICMJE	Infantile Hemangioma; Very Low Birth Weight Infants
Intervention ICMJE	Drug: topical 0.5% Timolol maleate topical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily; Drug: Control (placebo) group Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily
Study Arms	Experimental: Timolol Application of 1-2 drops of Timolol maleate 0.5% ophthalmic aqueous solution to hemangioma twice daily. Intervention: Drug: topical 0.5% Timolol maleate; Placebo Comparator: Placebo Application of 1-2 drops of placebo gel twice daily to hemangioma. Intervention: Drug: Control (placebo) group
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: January 12, 2016)	26
Original Estimated Enrollment ICMJE; (submitted: September 14, 2011)	42
Actual Study Completion Date	April 2016
Actual Primary Completion Date	April 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Babies admitted to NICU or seen in follow clinic that have a diagnosis of hemangioma that is verified by Principal Investigator (PI) or Co-Principal Investigators. Exclusion Criteria: Babies with PHACES (Posterior fossa, Hemangioma, Arterial lesions, Cardiac abnormalities, Eye abnormalities) syndrome; Babies with cardiac conditions that may predispose to heart block; Babies with persistent hypoglycemia; Babies on medications that may interact with beta blockers; Babies who are hemodynamically unstable and are requiring pressors to maintain blood pressure; Babies who are on systemic corticosteroid therapy
Sex/Gender	Sexes Eligible for Study: All
Ages	up to 6 Months (Child)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01434849
Other Study ID Numbers ICMJE	HSC20110333H
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: No Plan Description: Many participants did not complete trial so there is not enough data to share.
Responsible Party	Alice K. Gong, The University of Texas Health Science Center at San Antonio
Study Sponsor ICMJE	Alice K. Gong
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Alice K Gong, M.D. The University of Texas Health Science Center at San Antonio Study Director: Alice K Gong, MD University of Texas
PRS Account	The University of Texas Health Science Center at San Antonio
Verification Date	November 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP