A Clinical Trial of Pulsed-dye Laser Versus Timolol Topical Solution Versus Observation on the Growth of Hemangioma in Newborn

NCT01873131 | Recruiting

• 1 other identifier: 2010-P-001538
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if pulsed dye laser treatment or timolol maleate 0.5% gel can help infants who have a hemangioma. The investigators also want to find out if pulsed dye laser treatment and timolol maleate 0.5% gel are safe to use without causing too many side effects. Hemangioma is a common type of birthmark. These birthmarks happen when many new blood vessels grow in a specific area on the skin. Blood vessels are tiny tubes that carry blood through the body. No one knows what causes blood vessels to group together. Most birthmarks don't hurt at all and they usually aren't a sign of any kind of illness. Lots of newborns have these birthmarks on their bodies, like between the eyebrows. These birthmarks usually disappear within the first few months to years of life. These birthmarks tend to disappear spontaneously. Most hemangiomas are not treated unless the hemangioma threatens the child's health, which occurs in about 1 in 3 children with hemagiomas. Pulsed dye laser is widely used in children, and is approved by the U.S. Food and Drug Administration (FDA) for treating hemangioma. The FDA has approved timolol maleate to treat glaucoma in adults, but the FDA has not approved timolol maleate to treat hemangiomas in children. About 7 infants with hemangiomas have received timolol maleate. The results so far show that timolol maleate may be helpful and safe in treating hemangiomas in infants. An important question being tested in this study is whether pulsed-dye laser or timolol maleate can prevent hemangioma from growing when used very early after birth.

Conditions

Hemangioma

Keywords

hemangioma; infantile hemangioma; pulsed dye laser; PDL; topical beta blocker; timolol maleate; timolol

Outcome Measures

Primary Outcomes (1)

• Proportion of lesions that are completely clear or with minimum residual signs

  The primary outcome measurement will be the proportion of lesions that are completely clear or with minimum residual signs (defined as faint macular erythema with no palpable component). Three independent assessors (blinded to patient allocation) will be asked to evaluate photographs at each study visit compared to baseline using a 100-mm visual analog scale (VAS). Improvement in lesion size, thickness and color relative to baseline will be assessed by three independent observers.

  2 years

Secondary Outcomes (1)

• Proportion of parents who consider their children to have a cosmetically acceptable outcome, functional improvement, need for additional treatment and any adverse reactions

  2 years

Study Arms (3)

Topical Timolol

EXPERIMENTAL

After verification of eligibility criteria and obtaining informed consent of parent/guardian, infants randomized to the timolol arm will receive twice daily topical application of a physician-specified amount of timolol maleate 0.5% ophthalmic solution (hereby referred to as topical timolol) for up to six months.

Drug: topical timolol maleate

Observation

NO INTERVENTION

After verification of eligibility criteria and obtaining informed consent of parent/guardian, infants randomized to the observation arm will be followed at study visits according to protocol.

Pulsed Dye Laser

EXPERIMENTAL

After verification of eligibility criteria and obtaining informed consent of parent/guardian, infants randomized to the pulsed dye laser arm will receive a series of six weekly to semi-weekly laser treatments treatments for up to 6 treatments with potential for reduced number of treatments if the hemangioma completely resolves. A 595-nm pulsed-dye laser (PDL, V-beam Perfecta, Candela Corp, Wayland, MA) with a dynamic cooling device (DCD) will be utilized for all treatments. This device is cleared by the FDA for clinical treatment of vascular lesions.

Device: Pulsed dye laser

Interventions

topical timolol maleate DRUG

Timolol maleate 0.5% ophthalmic solution will be used. The dose will be 1 drop per square centimeter of hemangioma, rubbed into the area by the parent/guardian twice daily. The intent is to cover the entire lesion without excess of medication. Therefore, the dose can be lowered from 1 drop/cm2 at the discretion of the investigators, but not increased. This dose should not have significant systemic side effects given that the normal systemic intravenous dose for propanolol is 2mg/kg/day and there would be much less systemic absorption if the solution is applied topically. It is well established that the stratum corneum greatly slows the transport of timolol.

Also known as: timolol, beta blocker

Topical Timolol

Pulsed dye laser DEVICE

A 595-nm PDL (V-beam Perfecta, Candela Corp, Wayland, MA, USA) with a dynamic cooling device (DCD) will be utilized for all treatments. This device is cleared by the FDA for clinical treatment of vascular lesions. Protective eyewear for patient and all participants in the treatment room will be provided. A spot size of 7 or 10 mm will be used with an average fluence (energy delivered per unit area, in J/cm2) of 9 J/cm2 (range 8-10.0 J/cm2). Fluence will vary according to patient and hemangioma characteristics, including age, skin type, location, lesion thickness and response to treatment. A 30-50 ms cryogen spray cooling (CSC) duration will precede the laser pulse duration of 0.4 ms.

Also known as: PDL

Pulsed Dye Laser

Eligibility Criteria

• Age: Up to 3 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects aged less than 3 months, male or female.
• Infant with one or more superficial hemangiomas in the preproliferative phase or very early proliferative growth phase.
• Absence or minimal appearance of the lesion at birth
• More pronounced appearance within 1 month of birth.
• Willingness of parent/guardian to participate in the study
• Willingness of parent/guardian to receive EXPERIMENTAL treatment
• Informed consent agreement signed by the parent/guardian
• Willingness of parent/guardian to follow the treatment schedule and post treatment care requirements
• Willingness of parent/guardian to not use topical or systemic (oral) TREATMENT medications of the hemangioma other than those prescribed by the investigators during the study period.

You may not qualify if:

• Infants already on other treatment prior to PDL or timolol treatments (including topical, systemic steroids or other agents)
• Any infant who, in the opinion of his or her pediatrician or the investigators, has a major medical problem (such as cardiac pathology or airway obstruction) that makes participation in the study difficult
• Infants with hemangiomas that threaten vital functions (e.g. obstructing the airway or impairing hearing or vision)
• Scarring or infection of the area to be treated
• Subjects who are immunocompromised
• Subject whose parent/guardian is unable to comply with treatment, home care or follow-up visits
• Patients with asthma or a history of asthma, chronic obstructive pulmonary disease or cardiovascular disease, including sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, and cardiogenic shock; hypersensitivity to any component of timolol; and in those patients receiving systemic administration of beta-blockers or ace inhibitors.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Links

• wellman center link

MeSH Terms

Conditions

Hemangioma; Hemangioma, Capillary

Interventions

Timolol; Adrenergic beta-Antagonists; Lasers, Dye

Condition Hierarchy (Ancestors)

Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Lasers; Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies

Study Officials

• R. Rox Anderson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thanh Nga T Tran, MD PhD

CONTACT

617 724-4937; ttran2@partners.org

Yakir Levin, MD

CONTACT

617 724-4937; YLEVIN2@PARTNERS.ORG

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Wellman Center for Photomedicine

Study Record Dates

• First Submitted: August 20, 2012
• First Posted: June 7, 2013
• Study Start: February 1, 2011
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 2, 2023

Record last verified: 2023-11

Locations

US (1)