Nadolol Versus Propranolol in Children With Infantile Hemangiomas

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of oral propranolol versus nadolol in patients with Infantile Hemangiomas (IH) in a randomized, controlled, double-blinded study.

Detailed Description
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The study objective is to compare the efficacy and safety of oral propranolol in comparison with oral nadolol in patients with IH. Patients will be randomly assigned to either propranolol or dose equivalent nadolol. The duration of the study will be 24 weeks, however, patient will be monitored for up to 1 year post study enrolment. Both efficacy and safety will be closely monitored and captured.

Official Title
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Nadolol Versus Propranolol in Children With Infantile Hemangiomas: a Randomized, Controlled, Double-blinded Trial

Conditions
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Infantile Hemangioma

Intervention / Treatment
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* Drug: Nadolol
* Drug: Propranolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1-6 months corrected age Written parental informed consent At least one of the following: Size: hemangioma >1.5 cm on the face or >3 cm on other body parts Causing or with potential for functional impairment (e.g. amblyogenic IH, ulcerated hemangioma) Causing or with potential for cosmetic disfigurement (e.g. nasal tip, glabella location) Exclusion Criteria: Contraindications to beta-blockers Hypotension Bradycardia Hypoglycemia Cardiac disease associated with decreased ejection fraction and/or > second degree heart block Bronchospasm (including bronchial asthma) Allergic rhinitis Corrected gestational age less than 1 month at screening Patients with PHACES cerebral arteriopathy at risk of stroke Patients and/or breastfeeding mothers receiving treatment with anti-arrhythmic agents, calcium channel blockers, ACE inhibitors, inotropic agents, vasodilators, hypoglycemic agents, neuroleptics, antiacids, benzodiazepines, thyroxine, warfarin Patients treated with an oral beta-blocker or other agent (e.g. systemic steroids, vincristine) within 2 weeks from randomization Patients treated with topical timolol within 1 week from randomization Vascular tumors other than infantile hemangioma (e.g. pyogenic granuloma, hemangioendothelioma)

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nadolol group<br>40 study participants will take Nadolol (oral liquid suspension) | Drug: Nadolol<br>* Patients will be administered twice-daily doses of medication as follows: since Day 0- 0.5 mg/kg/day ; since Day 7-1.0 mg/kg/day and since Day 14- 1.5 mg/kg/day. In all subsequent visits the dosage will be adjusted based on the current weight rather than the baseline weight to maintain 1.5 mg/kg/day. Or the dose may be escalated (by 0.5 mg/kg/day at any following study visit) up to 3 mg/kg/day based on the clinical response to maintain the dose that led to at least 75% reduction in the hemangioma size until Week 24, when unblinding happen. At Week 24 paticipants can start weaning by 10% per week or continue with the last dose, depending on the investigator's decision. S/he will be monitored until Week 52.<br>* Other names: N/A (any brand );|
| Active Comparator: Propranolol group<br>40 study paticipants will take Propranolol (oral liquid suspension) | Drug: Propranolol<br>* Patients will be administered twice-daily doses of medication as follows: since Day 0- 0.5 mg/kg/day ; since Day 7-1.0 mg/kg/day and since Day 14- 1.5 mg/kg/day. In all subsequent visits the dosage will be adjusted based on the current weight rather than the baseline weight to maintain 1.5 mg/kg/day. Or the dose may be increased by investigator, based on clinical response by 0.5 mg/kg/day at any study visit (up to 3 mg/kg/day divided twice a day) to maintain the dose that lead to at least 75% reduction in the hemangioma size until Week 24, when unblinding happen. At Week 24 paticipants can start weaning by 10% per week or continue with the last dose, depending on the investigator's decision. S/he will be monitored until Week 52.<br>* Other names: N/A (any brand);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the bulk (size/extent) and color of the infantile hemangioma (IH)at Week 24 compared to baseline using Visual Analog Scale (VAS). | A 100 mm visual analog scale (VAS) will be used to quantify changes in the visible bulk (size/extent) and color of the lesion by comparing clinical photographs at 24 weeks versus baseline | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in IH bulk using VAS at 4, 12, 52 weeks | A 100 mm visual analog scale (VAS) will be used to quantify changes in the visible bulk (size/extent) of the lesion by comparing clinical photographs at weeks 4, 12, and 52 versus baseline | 4, 12, 52 weeks | 
| Time and dose to reach the 50%, 75% and 100% tumor shrinkage | Time frame since the baseline and study medication dose, when patient's IH decreased in size by 50%, 75% and 100%. | 52 weeks | 
| Inter-rater reliability of the VAS scores | Two raters will assess the changes in IH for each study patient ( each visit). We will compare these results to assess inter-rater reliability. | 52 weeks | 
| Percentage of patients achieving functional correction at Week 4, 12, 24, 52 | Percentage of patients achieving functional correction at Week 4, 12, 24, 52 | 4,12,24,52 weeks | 
| Percent change in the volumetric changes of hemangioma | [(Length + Width)/2]3 X 0.07 | 24 and 52 weeks | 
| Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma) | Percentage of patients with residual changes | 52 weeks | 
| Frequency of observed and reported adverse events | Frequency of observed and reported adverse events | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemangioma, propranolol, nadolol