Nadolol Versus Propranolol in Children With Infantile Hemangiomas

NCT ID: NCT02505971

Last Updated: 2020-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2020-06-30

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.

Conditions

Infantile Hemangioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nadolol group

40 study participants will take Nadolol (oral liquid suspension)

Group Type: ACTIVE_COMPARATOR

Nadolol

Intervention Type: 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.

Propranolol group

40 study paticipants will take Propranolol (oral liquid suspension)

Group Type: ACTIVE_COMPARATOR

Propranolol

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

N/A (any brand ); N/A (any brand)

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)

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Elena Pope

Section Head, Dermatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elena Pope, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 34747977 (View on PubMed)

Other Identifiers

1000048673

Identifier Type: -

Identifier Source: org_study_id