Infantile HemangiomaPhase 3NCT02505971
Nadolol Versus Propranolol in Children With Infantile Hemangiomas
A Phase 3 study testing Nadolol and Propranolol in people with Infantile Hemangioma, run by The Hospital for Sick Children at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 1 month to 6 months
- Conditions the study is for
- Infantile Hemangioma
- What is being tested?
- Nadolol and Propranolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2015to 30 Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- Contraindications to beta-blockers
- Hypotension
- Bradycardia
- Hypoglycemia
- Cardiac disease associated with decreased ejection fraction and/or > second degree heart block
- Bronchospasm (including bronchial asthma)
Show all 13Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nadolol Versus Propranolol in Children With Infantile Hemangiomas: a Randomized, Controlled, Double-blinded Trial
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.
Read the 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
- Being tested
- Nadolol, Propranolol
- Keywords
- hemangioma, propranolol, nadolol
- Medical subject headings
- Hemangioma, Capillary, Hemangioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NadololDrug
Also called N/A (any brand )
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.
PropranololDrug
Also called N/A (any brand)
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.
| Study group | Role | What they receive |
|---|---|---|
| Nadolol group | Active comparator | 40 study participants will take Nadolol (oral liquid suspension) Receives: Drug: Nadolol |
| Propranolol group | Active comparator | 40 study paticipants will take Propranolol (oral liquid suspension) Receives: Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 weeks
Secondary outcomes (7)
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
Measured: 4, 12, 52 weeks
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%.
Measured: 52 weeks
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.
Measured: 52 weeks
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Measured: 4,12,24,52 weeks
Percent change in the volumetric changes of hemangioma
[(Length + Width)/2]3 X 0.07
Measured: 24 and 52 weeks
Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma)
Percentage of patients with residual changes
Measured: 52 weeks
Frequency of observed and reported adverse events
Frequency of observed and reported adverse events
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study startSep 2015
- Primary completionApr 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infantile HemangiomaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elena Pope, The Hospital for Sick Children
- Investigators
- Elena Pope, MD, MSc, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02505971
- Sponsor's protocol ID
- 1000048673
- Status last verified
- Oct 2020
- First submitted
- 21 Jul 2015
- Last updated
- 28 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 34747977
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nadolol Versus Propranolol in Children With Infantile Hemangiomas: a Randomized, Controlled, Double-blinded Trial
- ClinicalTrials.gov ID
- NCT02505971
- Acronym / sponsor ID
- 1000048673
- Conditions
- Infantile Hemangioma
- Keywords
- hemangioma, propranolol, nadolol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Apr 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 22 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nadolol group | Active comparator | Drug: Nadolol40 study participants will take Nadolol (oral liquid suspension) |
| Propranolol group | Active comparator | Drug: Propranolol40 study paticipants will take Propranolol (oral liquid suspension) |
Who may qualify
- Ages
- 1 month to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 1-6 months corrected age
- Written parental informed consent
- At least one of the following:
Key exclusion criteria (13 listed)
- Contraindications to beta-blockers
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NadololAlso: N/A (any brand )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. | Drug | Nadolol group |
| PropranololAlso: N/A (any brand)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. | Drug | Propranolol group |
Primary outcome
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).
Time frame: 24 weeks
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
7 secondary outcomes
Percent change in IH bulk using VAS at 4, 12, 52 weeks
Time frame: 4, 12, 52 weeks
Time and dose to reach the 50%, 75% and 100% tumor shrinkage
Time frame: 52 weeks
Inter-rater reliability of the VAS scores
Time frame: 52 weeks
Percentage of patients achieving functional correction at Week 4, 12, 24, 52
Time frame: 4,12,24,52 weeks
Percent change in the volumetric changes of hemangioma
Time frame: 24 and 52 weeks
Percentage of patients with residual changes (telangiectasias, discoloration, fibro-fatty changes, anetoderma)
Time frame: 52 weeks
Frequency of observed and reported adverse events
Time frame: 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2020.
- Derived from this study: PubMed 34747977Pope 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.
Related trials for Infantile Hemangioma
Enrolling by invitation
Vbeam Pro Pulse Dye Laser for the Treatment of Vascular Conditions
Rosacea, Vascular Diseases
RecruitingPhase 4
68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
CNS Tumors, Meningioma
Not yet recruitingPhase 2
Rapamycin Dose-Ranging Efficacy Study in Port Wine Stains
Port Wine Stains
Active, not recruitingPhase 2
Agnostic Therapy in Rare Solid Tumors
Urachal Cancer, Parathyroid Carcinoma
RecruitingPhase 2/3
Efficacy and Safety of Different Initial Doses of Oral Propranolol in the Treatment of Ulcerated Infantile Hemangioma
Infantile Hemangioma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena Pope, MD, MSc principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nadolol and Propranolol in people with Infantile Hemangioma, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02505971, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2020.