Study to Demonstrate the Efficacy and Safety of Propranolol Oral Solution in Infants With Proliferating Infantile Hemangiomas Requiring Systemic Therapy

Infantile Hemangioma Clinical Trial

Official title:

A Randomised, Controlled, Multidose, Multicentre, Adaptive Phase II/III Study in Infants With Proliferating Infantile Hemangiomas (IHs) Requiring Systemic Therapy to Compare 4 Regimens of Propranolol (1 or 3 mg/kg/Day for 3 or 6 Months) to Placebo (Double Blind).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01056341
• Other study ID #: V00400 SB 201 Study
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 24, 2010
• Last updated: November 12, 2015
• Start date: January 2010
• Est. completion date: November 2013

Study information

• Verified date: November 2015
• Source: Pierre Fabre Dermatology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthSpain: Ministry of HealthRomania: National Medicines AgencyPeru: Instituto Nacional de SaludMexico: Federal Commission for Sanitary Risks ProtectionNew Zealand: Ministry of HealthAustralia: Department of Health and Ageing Therapeutic Goods AdministrationPoland: Ministry of HealthCzech Republic: State Institute for Drug ControlHungary: National Institute of PharmacyLithuania: State Medicine Control Agency - Ministry of HealthRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

There is an unsatisfied medical need for a first-line treatment of proliferating IHs with a good benefit/risk profile. Based on the recent findings of encouraging results obtained with propranolol in a series of infants with severe Infantile Hemangioma (IH), propranolol is expected to be of significant benefit in the management of the condition. The present study has been designed to confirm efficacy of propranolol in severe IH by demonstrating superiority over placebo and to document the safety profile of propranolol in this indication.

Description:

Primary objective The primary objective of this study is to identify the appropriate dose and duration of propranolol treatment and demonstrate its superiority over placebo based on the complete/nearly complete resolution of target IH at W24.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 512
• Est. completion date: November 2013
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Days to 150 Days

Eligibility

Inclusion Criteria:

• Proliferating IH (target hemangioma) requiring systemic therapy anywhere on the body except on the diaper area with largest diameter of at least 1.5 cm

Exclusion Criteria:

• The patient presents with one or more of the following medical conditions: Congenital hemangioma; Kasabach-Merritt syndrome; bronchial asthma; bronchospasm; hypoglycaemia (< 40 mg/dl or at risk); untreated phaeochromocytoma; hypotension (< 50/30 mmHg); second or third degree heart block; cardiogenic shock; metabolic acidosis; bradycardia (< 80 bpm); severe peripheral arterial circulatory disturbances; Raynaud's phenomenon; sick sinus syndrome; uncontrolled heart failure or Prinzmetal's angina; documented PHACES syndrome with central nervous system involvement

• The patient has previously been treated for IH, including any surgical and/or medical procedures (e.g. laser therapy)

• The patient is known to have a hypersensitivity to propranolol and/or any other beta-blockers

• One or more of the following types of IH are present:

• Life-threatening IH

• Function-threatening IH (e.g. those causing impairment of vision, respiratory compromise caused by airway lesions, etc.)

• Ulcerated IH (whatever the localisation) with pain and lack of response to simple wound care measures

• The patient was born prematurely and has not yet reached his/her term equivalent age (e.g. an infant born 2 months prematurely cannot be included before the age of 2 months)

• LVEF (left ventricular systolic function) =40% and/or cardiomyopathy and/or hereditary arrhythmia disorder

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemangioma
• Hemangioma, Capillary
• Infantile Hemangioma
• Port-Wine Stain

Intervention

Drug:
• Propranolol
Propranolol (1 or 3 mg/kg/day for 3 or 6 months)
• Placebo
Treatment with placebo for 6 months

Locations

Country	Name	City	State
Australia	Eastern Clinical Research Unit - Box Hill Hospital	Box Hill
Australia	Royal Children's Hospital	Melbourne
Australia	Sydney Children's Hospital	Randwick
Canada	CHU St.Justine	Montreal
Canada	The Hospital for Sick Children	Toronto
Czech Republic	Children Dermatology	Brno
Czech Republic	Clinic of Dermatovenerology, University	Prague
France	Hôpital Pellegrin-Enfants	Bordeaux
France	Hôpital Femme Mère Enfant	Lyon
France	CHU Hôtel Dieu	Nantes
France	Hôpital Archet 2	Nice
France	Hôpital Armand Trousseau	Paris
France	Hôpital Necker Enfants malades	Paris
France	Hopital Robert Debre - Consultation de Dermatologie	Paris
France	Hopital Nord-CHU St Etienne	St-Etienne
France	Hôpital des enfants	Toulouse
France	Hôpital Clocheville	Tours
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Kinderkrankenhaus Wilhelmstift	Hamburg
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Kinderchirurgische Klinik Ludwig-Maximilians-Universität	München
Hungary	Heim Pál Gyermekkórház,	Budapest
Italy	University of Bari	Bari
Italy	Clinica Dermatologica	Milano
Lithuania	Vilnius University Children's Hospital	Vilnius
Mexico	Hospital Infantil de Mexico Federico Gomez	Mexico CIty
New Zealand	Auckland Dermatology	Auckland
New Zealand	Waikato Clinical Research 2008 Ltd.	Hamilton
Peru	Clinica Internacional	Lima
Peru	Hospital Nacional Edgardo Rebagliati Martins	Lima
Peru	Instituto Nacional de Salud del Niño	Lima
Poland	Klinika Chirurgii i Urologii Dzieci i Mlodziezy Akademii Medycznej	Gdansk
Poland	University Children's Hospital	Krakow
Poland	Department of Pediatric Surgery and Oncology	Lodz
Poland	Klinika Onkologii, Centrum Zdrowia Dziecka	Warszawa
Romania	I.O.M.C Alfred Rusescu	Bucharest
Romania	Spitalul Clinic Urgenta pentru Copii Grigore Alexandrescu	Bucharest
Romania	Spitalul de Copii Dr. Victor Gomoiu	Bucharest
Romania	Spitalul Clinic de Urgenta pentu Copii Sf. Maria	Iasi
Romania	Spitalul de Urgenta Copii, Louis Turcanu	Timisoara
Russian Federation	Medical University - Filatov Pediatric Hospital	Moscow
Russian Federation	Medical Pediatric Academy	St-Peterburg
Russian Federation	Neonatal Intensive Care Department	St-Peterburg
Spain	Servicio de Dermatologia del Hospital Infantil	A Coruna
Spain	Hospital Sant Pau de Barcelona	Barcelona
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario Infantil Niño Jesús	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario de Valencia	Valencia
United States	Dell Children's Medical center	Austin	Texas
United States	State University of NY	Brooklyn	New York
United States	Children's Memorial Hospital	Chicago	Illinois
United States	University of California	Irvine	California
United States	Miami Children's Hospital	Miami	Florida
United States	Oregon Health Sciences University	Portland	Oregon
United States	Lucile Packard Children's Hospital	Redwood City	California
United States	Rady Children's Hospital	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Cardinal Glennon Children's Hospital	St.Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Pierre Fabre Dermatology

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Lithuania,  Mexico,  New Zealand,  Peru,  Poland,  Romania,  Russian Federation,  Spain, 

References & Publications (3)

Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. — View Citation

Léauté-Labrèze C, Hoeger P, Mazereeuw-Hautier J, Guibaud L, Baselga E, Posiunas G, Phillips RJ, Caceres H, Lopez Gutierrez JC, Ballona R, Friedlander SF, Powell J, Perek D, Metz B, Barbarot S, Maruani A, Szalai ZZ, Krol A, Boccara O, Foelster-Holst R, Feb — View Citation

Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, Lipsker D, Dupuis E, Ezzedine K, Vergnes P, Taïeb A, Léauté-Labrèze C. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics. 2009 Sep;124(3):e423-31. doi: 10.1542/peds.2008-3458. Epub 2009 Aug 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interim Analysis : Complete/Nearly Complete Resolution of the Target Infantile Hemangioma at Week 24 Compared to Baseline Based on the Intra-patient Blinded Centralized Independent Qualitative Assessments of Week 24 Photographs.		6 months	No
Primary	Primary Analysis : Complete/Nearly Complete Resolution of the Target Infantile Hemangioma at W24 Compared to Baseline Based on the Intra-patient Blinded Centralized Independent Qualitative Assessments of W24 Photographs.		6 months	No
Secondary	Success/Failure Based on the Investigator Qualitative Assessment of Complete Resolution at W48.	Time to first sustained improvement based on centralized qualitative assessments of paired patient-visits	6 months	No