search
Back to results

Nadolol Versus Propranolol in Children With Infantile Hemangiomas

Primary Purpose

Infantile Hemangioma

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Nadolol
Propranolol
Sponsored by
The Hospital for Sick Children
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infantile Hemangioma focused on measuring hemangioma, propranolol, nadolol

Eligibility Criteria

1 Month - 6 Months (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Nadolol group

Propranolol group

Arm Description

40 study participants will take Nadolol (oral liquid suspension)

40 study paticipants will take Propranolol (oral liquid suspension)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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%.
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.
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Percent change in the volumetric changes of hemangioma
[(Length + Width)/2]3 X 0.07
Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma)
Percentage of patients with residual changes
Frequency of observed and reported adverse events
Frequency of observed and reported adverse events

Full Information

First Posted
July 21, 2015
Last Updated
October 27, 2020
Sponsor
The Hospital for Sick Children
search

1. Study Identification

Unique Protocol Identification Number
NCT02505971
Brief Title
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

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
April 2020 (Actual)
Study Completion Date
June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infantile Hemangioma
Keywords
hemangioma, propranolol, nadolol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nadolol group
Arm Type
Active Comparator
Arm Description
40 study participants will take Nadolol (oral liquid suspension)
Arm Title
Propranolol group
Arm Type
Active Comparator
Arm Description
40 study paticipants will take Propranolol (oral liquid suspension)
Intervention Type
Drug
Intervention Name(s)
Nadolol
Other Intervention Name(s)
N/A (any brand )
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Propranolol
Other Intervention Name(s)
N/A (any brand)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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).
Description
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
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Percent change in IH bulk using VAS at 4, 12, 52 weeks
Description
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
Time Frame
4, 12, 52 weeks
Title
Time and dose to reach the 50%, 75% and 100% tumor shrinkage
Description
Time frame since the baseline and study medication dose, when patient's IH decreased in size by 50%, 75% and 100%.
Time Frame
52 weeks
Title
Inter-rater reliability of the VAS scores
Description
Two raters will assess the changes in IH for each study patient ( each visit). We will compare these results to assess inter-rater reliability.
Time Frame
52 weeks
Title
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Description
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Time Frame
4,12,24,52 weeks
Title
Percent change in the volumetric changes of hemangioma
Description
[(Length + Width)/2]3 X 0.07
Time Frame
24 and 52 weeks
Title
Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma)
Description
Percentage of patients with residual changes
Time Frame
52 weeks
Title
Frequency of observed and reported adverse events
Description
Frequency of observed and reported adverse events
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elena Pope, MD, MSc
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
34747977
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.
Results Reference
derived

Learn more about this trial

Nadolol Versus Propranolol in Children With Infantile Hemangiomas

We'll reach out to this number within 24 hrs