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

Hemangiomas affect 5-10% of all children born in the United States and up to 20% of premature
infants, with a higher incidence in girls. Most infantile hemangiomas (IHs) appear within a
few weeks of birth, grow rapidly for months to years and eventually involute. "Benign
neglect" (no treatment) is therefore recommended by most pediatricians. However, about 1/3 of
cases (2-3% of all children born in the US) eventually require medical or surgical
interventions for hemangiomas due to blocked vision, problems with breathing, feeding, pain,
ulceration, infection, profuse bleeding or disfigurement. None of the interventions are
benign. Occasionally, hemangiomas may be fatal.

The broad objective of this study is to prevent injury and disfigurement of millions of
children per year by developing a very safe, effective, and non-invasive treatment that
inhibits the growth of cutaneous hemangiomas in newborns. Historically, pulsed dye laser has
been known to bea very effective and safe treatment for hemangiomas; however, this treatment
modality has not been studied for the treatment of very early hemangiomas. Recently, systemic
beta-blockade with propanolol has also shown remarkable results in treating threatening
hemangiomas. However, systemic propanolol is not benign and requires inpatient monitoring for
cardiac side effects. Topical beta-blocker has been demonstrated in a case report to prevent
the growth of infantile eyelid hemangioma. We propose a prospective, single blinded,
randomized study of pulsed dye laser (PDL) and topical beta-blocker solution (timolol maleate
ophthalmic gel forming solution) in the treatment of very early hemangiomas. Specifically the
efficacy, side effects and outcome of PDL and timolol will be compared with no treatment, the
present standard of care for early stage hemangiomas. The extent to which early laser
treatment or topical timolol treatment prevents tumor growth and the need for future medical
or surgical treatments will be determined. Infants will be recruited from the pediatric and
neonatal practices at Massachusetts General Hospital, and randomized to receive either: (1) a
series of weekly to semi-weekly laser treatments, (2) twice daily topical application of
timolol ophthalmic gel-forming solution for six weeks, or (3) no treatment. Hemangiomas will
be assessed clinically and with digital photography for serial repeated measures of
hemangioma size at each study visit. A panel of blinded evaluators will also provide
assessment from photographs. Response, side effects and need for additional treatments will
be recorded for up to 2 years after PDL and topical timolol treatment. This clinical trial
fills a large gap in evidence-based medical therapy for IHs. If indeed early laser treatment
of hemangiomas with PDL or topical timolol, both relatively harmless treatments, can
eliminate the potential for complications by treating hemangiomas prior to the growth phase,
then this trial would present an attractive solution for the problem of when and how to
treat.

Inclusion Criteria:

1. Subjects aged less than 3 months, male or female.

2. Infant with one or more superficial hemangiomas in the preproliferative phase or very
early proliferative growth phase.

3. Absence or minimal appearance of the lesion at birth

4. More pronounced appearance within 1 month of birth.

5. Willingness of parent/guardian to participate in the study

6. Willingness of parent/guardian to receive EXPERIMENTAL treatment

7. Informed consent agreement signed by the parent/guardian

8. Willingness of parent/guardian to follow the treatment schedule and post treatment
care requirements

9. 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.

Exclusion Criteria:

1. Infants already on other treatment prior to PDL or timolol treatments (including
topical, systemic steroids or other agents)

2. 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

3. Infants with hemangiomas that threaten vital functions (e.g. obstructing the airway or
impairing hearing or vision)

4. Scarring or infection of the area to be treated

5. Subjects who are immunocompromised

6. Subject whose parent/guardian is unable to comply with treatment, home care or
follow-up visits

7. 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.