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

Primary Purpose

Hemangioma

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
topical timolol maleate
Pulsed dye laser
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hemangioma focused on measuring hemangioma, infantile hemangioma, pulsed dye laser, PDL, topical beta blocker, timolol maleate, timolol

Eligibility Criteria

undefined - 3 Months (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Experimental

Arm Label

Topical Timolol

Observation

Pulsed Dye Laser

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of parents who consider their children to have a cosmetically acceptable outcome, functional improvement, need for additional treatment and any adverse reactions
Proportion of parents who consider their children to have a cosmetically acceptable outcome, functional improvement, need for additional treatment and any adverse reactions arising from PDL treatment or timolol treatment or occurring as a natural progression of the hemangioma including hyper- or hypo- pigmentation, ulceration, atrophy and hypertrophic scarring, pain associated with ulceration, infection, bleeding, and requirement for intra-lesional or systemic steroids or any other additional treatment will be recorded.

Full Information

First Posted
August 20, 2012
Last Updated
August 10, 2022
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01873131
Brief Title
A Clinical Trial of Pulsed-dye Laser Versus Timolol Topical Solution Versus Observation on the Growth of Hemangioma in Newborn
Official Title
Preventing Growth of Hemangioma Tumors in Newborn: A Prospective Randomized Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 2011 (undefined)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemangioma
Keywords
hemangioma, infantile hemangioma, pulsed dye laser, PDL, topical beta blocker, timolol maleate, timolol

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Topical Timolol
Arm Type
Experimental
Arm Description
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.
Arm Title
Observation
Arm Type
No Intervention
Arm Description
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.
Arm Title
Pulsed Dye Laser
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
topical timolol maleate
Other Intervention Name(s)
timolol, beta blocker
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Pulsed dye laser
Other Intervention Name(s)
PDL
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of lesions that are completely clear or with minimum residual signs
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Proportion of parents who consider their children to have a cosmetically acceptable outcome, functional improvement, need for additional treatment and any adverse reactions
Description
Proportion of parents who consider their children to have a cosmetically acceptable outcome, functional improvement, need for additional treatment and any adverse reactions arising from PDL treatment or timolol treatment or occurring as a natural progression of the hemangioma including hyper- or hypo- pigmentation, ulceration, atrophy and hypertrophic scarring, pain associated with ulceration, infection, bleeding, and requirement for intra-lesional or systemic steroids or any other additional treatment will be recorded.
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
3 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thanh Nga T Tran, MD PhD
Phone
617 724-4937
Email
ttran2@partners.org
First Name & Middle Initial & Last Name or Official Title & Degree
Yakir Levin, MD
Phone
617 724-4937
Email
YLEVIN2@PARTNERS.ORG
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R. Rox Anderson, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thanh Nga T Tran, MD PhD
Phone
617-724-4937
Email
ttran2@partners.org
First Name & Middle Initial & Last Name & Degree
Ray H Jalian, MD
Phone
617 724-4937
Email
hjalian@partners.org
First Name & Middle Initial & Last Name & Degree
R. Rox Anderson, MD
First Name & Middle Initial & Last Name & Degree
Thanh Nga T Tran, MD PhD
First Name & Middle Initial & Last Name & Degree
Kelly Stankiewicz, MD
First Name & Middle Initial & Last Name & Degree
Ray H Jalian, MD

12. IPD Sharing Statement

Links:
URL
http://wellman.massgeneral.org/research-clinicalstudies.htm
Description
wellman center link

Learn more about this trial

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

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