Propranolol Dosing Frequency for Infantile Hemangiomas

Overseen By Chioma Obinero

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Cardiac disease, Pulmonary disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different dosing schedules of propranolol, a medication, affect sleep patterns in infants with hemangiomas (a type of birthmark made of blood vessels). Researchers aim to determine if taking propranolol three times a day improves sleep more than the twice-a-day schedule or the control treatment, timolol (a topical medication). Infants with clinically diagnosed hemangiomas whose parents speak English or Spanish qualify as good candidates for this study. As a Phase 4 trial, propranolol is already FDA-approved and proven effective, and this research helps to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for propranolol and timolol?

Research has shown that propranolol is safe and effective for treating infantile hemangiomas, a type of birthmark. One study found that propranolol is safer than other treatments for these birthmarks. Most babies responded well to the treatment, experiencing few serious side effects. Common side effects might include lower blood pressure or heart rate, but these are usually mild and manageable.

The FDA has already approved propranolol for treating infantile hemangiomas, indicating a strong safety record for this condition. However, propranolol should not be used in certain cases, such as if a baby has a specific type of tumor called pheochromocytoma or is very underweight. Consulting a healthcare provider is essential to determine if propranolol is a suitable option. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it aims to determine the optimal dosing frequency of propranolol for treating infantile hemangiomas, a common type of birthmark made of blood vessels. While propranolol is already a standard treatment, the trial compares two dosing schedules: three times a day (TID) and twice a day (BID). Finding the most effective dosing schedule could improve patient convenience and adherence while maintaining or enhancing the treatment's effectiveness. This could be particularly beneficial for infants and their caregivers, easing the burden of frequent medication administration without compromising results.

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

Research has shown that propranolol effectively treats infantile hemangiomas (IH), common birthmarks in children. Studies indicate that more than 90% of infants improve their IH with propranolol. In one study, 22 out of 24 infants showed noticeable improvement in their birthmarks. Due to its high success rate, propranolol is often the first choice for treating IH. The medication narrows blood vessels and reduces blood flow to the hemangioma, helping it shrink and fade. This trial will compare different dosing frequencies of propranolol, with some participants receiving the medication three times a day and others twice a day, to determine the most effective regimen. ^{1 3 6 7 8}

Who Is on the Research Team?

Matthew R Greives, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for infants with diagnosed hemangiomas. Participants must have parents who consent to the study and can communicate in English or Spanish. Infants with significant heart or lung diseases that make it unsafe to take oral propranolol are not eligible.

Inclusion Criteria

I have been diagnosed with a hemangioma.

Exclusion Criteria

I cannot take oral propranolol due to severe heart or lung disease.

Parents who do not consent to the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral propranolol at BID or TID dosing regimen or timolol as a control

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Propranolol
• Timolol

Trial Overview

The study is testing how different dosing schedules of Propranolol (three times a day vs twice a day) affect sleep patterns in infants with hemangiomas, compared to a control group using Timolol.

How Is the Trial Designed?

Group I: ter in die (TID)three times a day Experimental Treatment 1 Intervention

Group II: bis in die (BID)twice a day Experimental Treatment 1 Intervention

Group III: Control Active Control 1 Intervention

Propranolol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• High blood pressure
• Angina pectoris
• Heart rhythm disorders
• Migraine prophylaxis
• Essential tremor
• Performance anxiety

Approved in European Union as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Approved in Canada as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study of 15 infants with problematic proliferating infantile haemangioma, propranolol was found to be effective and safe at a dosage of 1.5-2.0 mg/kg/day, leading to accelerated involution of the lesions.

Treatment should be continued until the hemangioma is fully involuted or the child reaches 12 months of age, as rebound growth was observed in one patient when treatment was stopped early, highlighting the importance of maintaining the treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose propranolol for infantile haemangioma. Tan, ST., Itinteang, T., Leadbitter, P.[2022]

Topical propranolol hydrochloride gel was found to be effective and safe for treating superficial infantile hemangiomas, with 44.83% of patients showing good improvement and 13.79% achieving excellent results based on a study of 51 cases.

The treatment demonstrated significantly better responses in superficial hemangiomas compared to other types, indicating its targeted efficacy, with no adverse effects reported during the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical propranolol hydrochloride gel for superficial infantile hemangiomas. Wang, L., Xia, Y., Zhai, Y., et al.[2021]

Propranolol is the preferred treatment for complicated Infantile Hemangiomas (IH), and a study involving 22 infants showed that a pediatric solution of propranolol at 3 mg/kg/day given twice daily (BID) is effective, with pharmacokinetics similar to adults.

The research established a population model for propranolol's pharmacokinetics, confirming that weight affects drug clearance but not volume of distribution, and simulations indicated that regular BID dosing is preferable to TID dosing, ensuring effective drug levels in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol pharmacokinetics in infants treated for Infantile Hemangiomas requiring systemic therapy: Modeling and dosing regimen recommendations. Del Frari, L., Léauté-Labrèze, C., Guibaud, L., et al.[2018]

Propranolol hydrochloride is commonly used and generally safe for treating infantile hemangiomas, but serious adverse effects, such as deep hypoglycemic coma, can occur, highlighting the need for vigilance during treatment.

Early recognition of potential adverse effects is critical for effective patient management, and educating both healthcare providers and parents is essential to ensure safety during propranolol therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep coma in a child treated with propranolol for infantile hemangioma. Bakalli, I., Kola, E., Lluka, R., et al.[2020]

Propranolol is an effective first-line treatment for infantile hemangioma (IH), with 83.4% of patients showing partial regression and 14.5% achieving total regression after a mean treatment duration of 6 months.

The treatment was generally safe, with only 21.7% of patients experiencing mild reactions and no life-threatening adverse effects reported, although one child had to interrupt therapy due to worsening asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol therapy in 55 infants with infantile hemangioma: dosage, duration, adverse effects, and outcome. Schupp, CJ., Kleber, JB., Günther, P., et al.[2022]

Atenolol is as effective as propranolol in treating infantile hemangiomas, with no significant difference in treatment outcomes based on a study of 27 children treated with atenolol compared to 53 treated with propranolol.

Atenolol has a better safety profile, as none of the patients experienced bronchospasm, a side effect seen in 11% of those treated with propranolol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study. Bayart, CB., Tamburro, JE., Vidimos, AT., et al.[2018]

Propranolol (PRN) is effective as a first-line treatment for complicated infantile hemangiomas (IHs), but this study provides new insights into how its administration frequency affects plasma concentration levels in infants.

A single daily dose of PRN (1 mg/kg/d) leads to a quicker rise in plasma levels compared to a twice-daily dose, which maintains levels longer, offering important pharmacokinetic information for optimizing treatment in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study on plasma RPN concentration of patients with infantile hemangioma treated with propranolol. Zhang, L., Mai, HM., Zheng, J., et al.[2021]

In a study of 245 patients with infantile hemangiomas (IH), those requiring higher doses of propranolol (≥2.5 mg/kg/d) were typically larger, located on the face, and had more complex mixed or deep morphology, indicating that these characteristics are associated with a poorer response to standard dosing.

Despite increasing the propranolol dosage, patients showed minimal improvement in their Hemangioma Activity Score, and over 26% of those on higher doses ultimately required surgical excision, suggesting that higher dosing may not be effective for all IH cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective case series of increased oral propranolol dosage for infantile hemangiomas. Huang, AH., Mannschreck, D., Aggarwal, P., et al.[2021]

Propranolol, administered at a dose of 2 mg/kg/day, was effective in treating a 4-cm infantile hemangioma in a 6-month-old infant, leading to near complete resolution in less than 6 months.

The treatment was well-tolerated with no reported side effects or relapses, indicating a safe and effective option for managing the growth phase of infantile hemangiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infantile Hemangioma Treated with Oral Propranolol: Case Presentation. Raufi, N., Nemat, A.[2021]

In a study of 108 infants treated with oral propranolol for infantile hemangiomas, the medication was found to cause statistically significant but asymptomatic decreases in blood pressure and heart rate, indicating it is generally safe for use in this population.

No arrhythmias were detected during treatment, and while mild sleep disturbances were noted in some infants, overall heart rhythm and circadian patterns remained stable, suggesting that extensive monitoring may not be necessary for safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral propranolol for infantile hemangiomas: a prospective study on the role of 48-hour Holter monitoring in additional safety assessment. Petrovic, J., Trifunovic, B., Vukomanovic, G., et al.[2018]

Citations

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Propranolol in the Treatment of Infantile Hemangiomas - PMC

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Propranolol: Uses, Dosage, Side Effects, Warnings

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Propranolol (Infantile Hemangioma)

Propranolol (Infantile Hemangioma): learn about side effects, dosage, special precautions, and more on MedlinePlus.

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Propranolol combined with laser in the treatment of infantile hemangiomas has remarkable short-term curative effects. It can effectively reduce the levels of ...