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

174 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the baseline sleep pattern disruption for patients starting oral propranolol at the standard BID dosing regimen compared to the control (timolol) group and to determine if there is a significant improvement in the sleep patterns in infants taking oral propranolol on the TID dosing regimen versus the control (timolol) group

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 data supports the effectiveness of the drug propranolol for treating infantile hemangiomas?

Research shows that propranolol is effective in treating infantile hemangiomas, with many patients experiencing significant improvement or complete healing. In one study, 83.4% of infants had partial regression and 14.5% had total regression of their hemangiomas after treatment with propranolol. ^{1 2 3 4 5}

Is propranolol safe for treating infantile hemangiomas?

Propranolol is generally considered safe for treating infantile hemangiomas, but it can have side effects like bronchospasm (breathing difficulty), hypoglycemia (low blood sugar), and sleep disturbances. Studies have shown that both oral and topical forms are effective and safe, though monitoring for side effects is important. ^{4 5 6 7 8}

How is the drug propranolol unique in treating infantile hemangiomas?

Propranolol is unique for treating infantile hemangiomas because it is the first-choice therapy and can be administered in a flexible twice-daily dosing schedule, which is effective and allows for irregular intervals if needed. It is also notable for its rapid effect on reducing the size and color of hemangiomas, with minimal side effects compared to other treatments. ^{1 2 4 9 10}

Research Team

Matthew R Greives, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 (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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Propranolol therapy in 55 infants with infantile hemangioma: dosage, duration, adverse effects, and outcome. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Infantile Hemangioma Treated with Oral Propranolol: Case Presentation. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Deep coma in a child treated with propranolol for infantile hemangioma. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Propranolol pharmacokinetics in infants treated for Infantile Hemangiomas requiring systemic therapy: Modeling and dosing regimen recommendations. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Preliminary study on plasma RPN concentration of patients with infantile hemangioma treated with propranolol. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study. [2018]

7. England 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. [2018]

8. China pubmed.ncbi.nlm.nih.gov

Topical propranolol hydrochloride gel for superficial infantile hemangiomas. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Retrospective case series of increased oral propranolol dosage for infantile hemangiomas. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Low-dose propranolol for infantile haemangioma. [2022]