Nadolol Versus Propranolol in Children With Infantile Hemangiomas

Infantile Hemangioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02505971
• Other study ID #: 1000048673
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: June 30, 2020

Study information

• Verified date: October 2020
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: June 30, 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 6 Months

Eligibility

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)

Related Conditions & MeSH terms

• Hemangioma
• Hemangioma, Capillary
• Infantile Hemangioma
• Port-Wine Stain

Intervention

Drug:
• Nadolol
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.
• Propranolol
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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percent change in the volumetric changes of hemangioma	[(Length + Width)/2]3 X 0.07	24 and 52 weeks
Secondary	Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma)	Percentage of patients with residual changes	52 weeks
Secondary	Frequency of observed and reported adverse events	Frequency of observed and reported adverse events	52 weeks