Low-Dose Propranolol and Bleomycin for Infantile Hemangioma (IH)

Evaluation of the Efficacy and Safety of Low-Dose Propranolol Combined With Intralesional Bleomycin for Infantile Hemangioma: A Randomized Controlled Trial

This is a prospective, randomized controlled trial designed to evaluate the efficacy and safety of low-dose oral propranolol (1 mg/kg/day) combined with monthly intralesional bleomycin injections versus low-dose propranolol monotherapy for the treatment of infantile hemangioma (IH). A total of 260 infants were randomized to either the combination group or the control group. The study aims to determine if the combination therapy offers superior clinical outcomes, including faster regression, better color resolution, and reduced scarring over a 6-month treatment period.

Study Overview

• Status: Completed
• Conditions: Infantile Hemangioma (IH)
• Intervention / Treatment: Drug: Propranolol + Bleomycin; Drug: Propranolol

Detailed Description

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy. While oral propranolol is the first-line systemic therapy, its efficacy can be limited or slow for certain IHs. Intralesional bleomycin offers a targeted local therapy. This study investigates whether combining low-dose propranolol with local bleomycin injections can enhance therapeutic effects while maintaining a good safety profile. This prospective, randomized, controlled, open-label trial with blinded outcome assessment enrolled 260 infants with IH. Participants were randomly assigned to receive either oral propranolol (1 mg/kg/day) plus monthly intralesional bleomycin (Combination Group) or oral propranolol (1 mg/kg/day) alone (Control Group) for 6 months. The primary objective is to compare the clinical therapeutic effect between the two groups at 6 months. Secondary objectives include evaluating early tumor response, changes in tumor volume and color, long-term scar formation, and the incidence of adverse events. The findings aim to provide robust evidence for a potentially more effective combination treatment strategy for IH.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430015
      • Wuhan Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≤12 months.
• Clinically and/or imaging-diagnosed infantile hemangioma requiring treatment.
• No prior treatment for IH.
• Guardians willing to comply with the study protocol and provide informed consent.

Exclusion Criteria:

• Known hypersensitivity to propranolol or bleomycin.
• Congenital or mixed hemangiomas distinct from IH.
• Significant cardiopulmonary, hepatic, or renal dysfunction.
• Presence of other severe systemic diseases.
• PHACE syndrome or major congenital anomalies that could interfere with treatment or assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Combination Therapy Group; Participants received oral propranolol hydrochloride solution at a dose of 1 mg/kg/day (in two divided doses) for 6 months, combined with intralesional injections of bleomycin. Bleomycin injections were administered once a month for up to 6 months.	Drug: Propranolol + Bleomycin; Oral propranolol at 1 mg/kg/day for 6 months plus intralesional bleomycin (1 mg/mL solution) injected once monthly. The bleomycin dose was 0.2-0.5 mg per injection site, not exceeding a total of 1 mg/kg per session or a cumulative dose of 10 mg.
Active Comparator: Active Comparator: Propranolol Monotherapy Group; Participants received oral propranolol hydrochloride solution at a dose of 1 mg/kg/day (in two divided doses). The total treatment duration was 6 months.	Drug: Propranolol; Oral propranolol hydrochloride solution administered at a dose of 1 mg/kg/day for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Therapeutic Effect	Categorized as Complete Regression (>95% volume reduction), Marked Effectiveness (≥75% to 95% volume reduction), Effective (30% to <75% reduction), or Ineffective (<30% reduction). The primary measure is the rate of participants achieving Complete Regression or Marked Effectiveness.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Tumor Surface Atrophy	Assessed by comparing photographs and graded as Obvious Atrophy, Mild Atrophy, or No Obvious Change.	24 hours after the first treatment
Change in Hemangioma Color Score	Rated on a 4-point subjective scale (0-3) based on standardized digital photographs, where a lower score indicates color closer to normal skin. The change from baseline is assessed.	Baseline, 6 Months
Change in Tumor Volume	Measured in cubic centimeters (cm³) using high-frequency color Doppler ultrasound (Volume = length × width × height × 0.52). The change from baseline is assessed.	Baseline, 6 Months
Vancouver Scar Scale (VSS) Score	Assessed at the former hemangioma site. The VSS evaluates pigmentation, vascularity, pliability, and height, with a total score from 0 (normal skin) to 13 (worst scar). Lower scores indicate better outcomes.	6 Months
Incidence of Adverse Events	Number and type of local and systemic adverse events reported by guardians or observed clinically (e.g., injection site reactions, bradycardia, hypoglycemia, sleep disturbances).	Through study completion (6 months)

Collaborators and Investigators

• Sponsor: Wuhan Integrated Traditional Chinese and Western Medicine Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): January 1, 2025
• Study Completion (Actual): January 1, 2025

Study Registration Dates

• First Submitted: July 29, 2025
• First Submitted That Met QC Criteria: July 29, 2025
• First Posted (Actual): August 5, 2025

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Congenital Abnormalities; Neoplasms, Vascular Tissue; Skin Abnormalities; Hemangioma; Hemangioma, Capillary; Port-Wine Stain; Antibiotics, Antineoplastic; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adrenergic Agents; Vasodilator Agents; Antihypertensive Agents; Adrenergic beta-Antagonists; Adrenergic Antagonists; Bleomycin; Propranolol
• Other Study ID Numbers: 2023R064-E01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No