Pulsed-dye Laser vs. Topical Timolol for Hemangioma

Overseen By Thanh Nga T Tran, MD PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Beta-blockers, Ace inhibitors

Disqualifiers: Asthma, Cardiovascular disease, Immunocompromised, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks to 6 months

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether pulsed dye laser treatment or timolol maleate 0.5% gel (a topical medication) can effectively treat hemangiomas, a common type of birthmark in infants. Researchers are exploring which treatment better prevents the growth of these birthmarks when used early. They also seek to ensure that both treatments are safe for infants and cause minimal side effects. Infants younger than three months with noticeable hemangiomas that became more visible within the first month of birth may be suitable for this trial, especially if their parents are willing to adhere to the study's requirements. As an unphased trial, this study provides a unique opportunity for parents to contribute to understanding effective early treatments for infant hemangiomas.

Will I have to stop taking my current medications?

The trial requires that participants do not use any other topical or oral treatments for the hemangioma besides those prescribed by the study investigators. If your infant is already on other treatments for hemangioma, they would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found pulsed-dye laser treatment highly effective for infantile hemangiomas, with improvements in up to 85% of cases. The treatment was generally well-tolerated, achieving a success rate of about 84.4% with few side effects.

Research has shown that topical timolol, originally used for glaucoma, is also effective for hemangiomas. Many studies indicate it is well-tolerated in infants, with minimal side effects. Although approved for a different condition, its use for hemangiomas in children remains under study.

Both treatments have demonstrated promising safety and effectiveness in earlier research, but ongoing studies aim to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for hemangiomas because they offer unique approaches compared to traditional therapies like oral propranolol or surgical intervention. Topical Timolol provides a non-invasive option, using a 0.5% ophthalmic solution applied directly to the skin, potentially reducing systemic side effects and offering convenience for caregivers. The Pulsed-dye Laser is notable for its precision, utilizing a 595-nm laser to target blood vessels in the hemangioma specifically, which might lead to faster resolution with fewer sessions. Both treatments represent innovative strategies that could improve safety and comfort for infants while delivering effective results.

What evidence suggests that this trial's treatments could be effective for hemangioma?

Research has shown that pulsed dye laser treatment, one of the treatments studied in this trial, effectively treats hemangiomas, a type of birthmark, in infants. It can improve up to 85% of surface-level cases. This treatment reduces the size of the birthmark and any swelling, and it accelerates healing with few side effects. Another treatment option in this trial is a gel called topical timolol, originally used for glaucoma, which can help with early-stage infant hemangiomas. While safe to use, it doesn't shrink the birthmarks as much. Both treatments show promise, but pulsed dye laser has stronger evidence for effectively managing hemangiomas. ^{1 2 3 4 6}

Who Is on the Research Team?

R. Rox Anderson, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for infants under 3 months old with a type of birthmark called hemangioma that appeared shortly after birth. The child must not have received any prior treatments, and the parents/guardians must agree to follow the study's treatment plan and care requirements.

Inclusion Criteria

The birthmark is very small or not visible.

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

My condition became noticeable within a month after birth.

Exclusion Criteria

You have a weakened immune system.

The area to be treated has scarring or infection.

I have asthma, COPD, heart issues, or am allergic to timolol. I also take beta-blockers or ACE inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Infants receive either pulsed dye laser treatments weekly to semi-weekly for up to 6 treatments, or twice daily topical application of timolol for up to six months

6 weeks to 6 months

Weekly to semi-weekly visits for laser treatment, or regular follow-ups for timolol application

Follow-up

Participants are monitored for safety, effectiveness, and need for additional treatments after the initial treatment phase

2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Observation
• Pulsed-dye Laser
• Topical Timolol Maleate

Trial Overview

The study tests if pulsed dye laser or timolol maleate gel can prevent the growth of hemangiomas in newborns. It compares these treatments against no intervention to see which is more effective and safe for treating these birthmarks early on.

How Is the Trial Designed?

Group I: Topical Timolol Experimental Treatment 1 Intervention

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.

Group II: Pulsed Dye Laser Experimental Treatment 1 Intervention

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.

Group III: Observation Active Control 1 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.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Topical timolol maleate (5 mg/mL) is a safe and effective treatment for superficial infantile hemangiomas, showing significant improvement in hemoglobin levels after an average of 4 months of treatment.

For mixed hemangiomas, combined sequential dual-wavelength laser treatment (pulsed dye and Nd:YAG) was more effective than timolol, as it penetrated deeper to target blood vessels, resulting in greater improvement over an average treatment duration of 5.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical timolol solution versus laser in treatment of infantile hemangioma: a comparative study. Tawfik, AA., Alsharnoubi, J.[2015]

In a study of 21 patients with superficial infantile hemangiomas, pulsed dye laser (PDL) treatment showed significantly better clinical improvement compared to topical timolol cream after an average of 3.39 treatment sessions over 2 months.

Both treatments were safe, with no patients experiencing permanent side effects, but the results suggest that PDL may be a more effective option for treating superficial proliferating hemangiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, open-label, rater-blinded and self-controlled pilot study of the treatment of proliferating superficial infantile hemangiomas with 0.5% topical timolol cream versus 595-nm pulsed dye laser. Ying, H., Zou, Y., Yu, W., et al.[2018]

Topical timolol gel 0.5% significantly improved infantile hemangiomas in 40 infants, with a median increase of 7 points on a visual analog scale after 5 months, indicating its efficacy as a treatment.

Systemic absorption of timolol was confirmed, with 83% of urine tests positive for the drug and low serum levels detected, suggesting that while the treatment is effective and generally safe, caution is needed for larger or ulcerated hemangiomas and very young infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Timolol for Infantile Hemangiomas: Evidence for Efficacy and Degree of Systemic Absorption. Weibel, L., Barysch, MJ., Scheer, HS., et al.[2017]

In a study involving 30 infants with infantile hemangioma, the combination of pulsed dye laser (PDL) treatment and timolol gel resulted in a significantly greater reduction in lesion size compared to PDL treatment alone.

The combination therapy not only showed higher efficacy in reducing hemangioma size but also provided better patient-reported outcomes, indicating it may be a more effective treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed dye laser and topical timolol gel versus pulse dye laser in treatment of infantile hemangioma: A double-blind randomized controlled trial. Asilian, A., Mokhtari, F., Kamali, AS., et al.[2020]

The combination of 595-nm pulsed-dye laser (PDL) and 0.5% timolol maleate solution is a safe and effective treatment for superficial infantile hemangioma (IH), with a high efficacy rate of 95.5% in patients treated early (≤2 months) compared to 86.1% in those treated later (>2 months).

Early intervention not only resulted in better treatment outcomes but also required fewer treatment sessions and was associated with a lower risk of permanent side effects, highlighting the importance of timely therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing and Efficacy of 595-nm Pulsed-Dye Laser Combined with 0.5% Timolol Maleate Solution in the Treatment of Superficial Infantile Hemangiomas. Shi, W., He, H., Jiang, J., et al.[2022]

Topical 0.25% timolol maleate gel is effective in treating nonvision-threatening infantile capillary hemangiomas, with 61.5% of treated infants showing a good response after 2 months, compared to 0% in the observation group.

The treatment was safe, with no adverse ocular or systemic effects reported, and the positive responses were stable over long-term follow-up, indicating its potential as a reliable option for managing these lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled study of topical 0.25% timolol maleate gel for the treatment of cutaneous infantile capillary hemangiomas. Chambers, CB., Katowitz, WR., Katowitz, JA., et al.[2018]

Topical beta-blocker timolol maleate 0.5% was effective in treating infantile hemangioma, showing a mean improvement of 47.0% based on physicians' assessments in a study of 102 patients.

When combined with pulsed dye laser treatment, the improvement increased to 66.5%, and importantly, no side effects were reported in either treatment group, highlighting the safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical timolol maleate 0.5% for infantile hemangioma; it's effectiveness and/or adjunctive pulsed dye laser - single center experience of 102 cases in Korea. Park, KH., Jang, YH., Chung, HY., et al.[2018]

Citations

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Comparative evaluation of laser therapy for infantile ...

Results. The 595-nm pulsed dye laser (PDL) was the most studied and showed high efficacy for superficial IHs, with improvement rates up to 85 ...

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Our study explores the timing and safety of 595‐nm pulsed dye laser (PDL) treatment for early superficial IH. We retrospectively analyzed 180 ...

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Conclusion: Pulsed dye laser treatment can promote the regression of skin lesions in infantile hemangioma, reduce the levels of inflammation and ...

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Combination Therapy of Infantile Hemangioma with Pulsed ...

Pulsed dye laser (PDL) as a modality of treatment for IH shows some controversies, but it is widely accepted for management of ulcerated hemangiomas.

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An exploration of optimal time and safety of 595-nm pulsed ...

The number of laser treatments and the occurrence of adverse reactions were recorded simultaneously. The overall effective and cure rates were 98.3% and 84.4%, ...