Clinical trial NCT02505971: Nadolol Versus Propranolol in Children With Infantile Hemangiomas
Official title: Nadolol Versus Propranolol in Children With Infantile Hemangiomas: a Randomized, Controlled, Double-blinded Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infantile Hemangioma
Keywords: hemangioma, propranolol, nadolol
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2015-07-22
Enrollment: 74
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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).
timeFrame: 24 weeks
Secondary outcomes:
measure: Percent change in IH bulk using VAS at 4, 12, 52 weeks
timeFrame: 4, 12, 52 weeks
measure: Time and dose to reach the 50%, 75% and 100% tumor shrinkage
timeFrame: 52 weeks
measure: Inter-rater reliability of the VAS scores
timeFrame: 52 weeks
measure: Percentage of patients achieving functional correction at Week 4, 12, 24, 52
timeFrame: 4,12,24,52 weeks
measure: Percent change in the volumetric changes of hemangioma
timeFrame: 24 and 52 weeks
measure: Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma)
timeFrame: 52 weeks
measure: Frequency of observed and reported adverse events
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Elena Pope, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.