Nadolol Versus Propranolol in Children With Infantile Hemangiomas

NCT02505971 | Completed Phase 3

• 1 other identifier: 1000048673
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Infantile Hemangioma

Keywords

hemangioma, propranolol, nadolol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Percent change in IH bulk using VAS at 4, 12, 52 weeks

  4, 12, 52 weeks

• Time and dose to reach the 50%, 75% and 100% tumor shrinkage

  52 weeks

• Inter-rater reliability of the VAS scores

  52 weeks

• 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

  24 and 52 weeks

Study Arms (2)

Nadolol group

ACTIVE COMPARATOR

40 study participants will take Nadolol (oral liquid suspension)

Drug: Nadolol

Propranolol group

ACTIVE COMPARATOR

40 study paticipants will take Propranolol (oral liquid suspension)

Drug: Propranolol

Interventions

Nadolol DRUG

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.

Also known as: N/A (any brand )

Nadolol group

Propranolol DRUG

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.

Also known as: N/A (any brand)

Propranolol group

Eligibility Criteria

• Age: 1 Month - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

Related Publications (1)

• Pope E, Lara-Corrales I, Sibbald C, Liy-Wong C, Kanigsberg N, Drolet B, Ma J. Noninferiority and Safety of Nadolol vs Propranolol in Infants With Infantile Hemangioma: A Randomized Clinical Trial. JAMA Pediatr. 2022 Jan 1;176(1):34-41. doi: 10.1001/jamapediatrics.2021.4565.

  PMID: 34747977 DERIVED

MeSH Terms

Conditions

Hemangioma, Capillary; Hemangioma

Interventions

Nadolol; Propranolol

Condition Hierarchy (Ancestors)

Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Elena Pope, MD, MSc

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Head, Dermatology

Study Record Dates

• First Submitted: July 21, 2015
• First Posted: July 22, 2015
• Study Start: September 1, 2015
• Primary Completion: April 1, 2020
• Study Completion: June 30, 2020
• Last Updated: October 28, 2020

Record last verified: 2020-10

Locations

CA (1)