Clinical trial NCT01056341: Study to Demonstrate the Efficacy and Safety of Propranolol Oral Solution in Infants With Proliferating Infantile Hemangiomas Requiring Systemic Therapy
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Infantile Hemangioma
Keywords: Infantile Hemangioma
Propranolol
Lead sponsor: Pierre Fabre Dermatology
Sponsor class: INDUSTRY
First posted: 2010-01-26
Enrollment: 512
Sex: ALL
Minimum age (years): 35
Maximum age (years): 150
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
Secondary outcomes:
measure: Success/Failure Based on the Investigator Qualitative Assessment of Complete Resolution at W48.
timeFrame: 6 months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California
state: California
city: Redwood City
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: St.Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Brooklyn
country: United States
facility: State University of NY
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Austin
country: United States
facility: Dell Children's Medical center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit - Box Hill Hospital
city: Melbourne
country: Australia
facility: Royal Children's Hospital
city: Randwick
country: Australia
facility: Sydney Children's Hospital
city: Montreal
country: Canada
facility: CHU St.Justine
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Brno
country: Czech Republic
facility: Children Dermatology
city: Prague
country: Czech Republic
facility: Clinic of Dermatovenerology, University
city: Bordeaux
country: France
facility: Hôpital Pellegrin-Enfants
city: Lyon
country: France
facility: Hôpital Femme Mère Enfant
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Nice
country: France
facility: Hôpital Archet 2
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Paris
country: France
facility: Hôpital Necker Enfants malades
city: Paris
country: France
facility: Hopital Robert Debre - Consultation de Dermatologie
city: St-Etienne
country: France
facility: Hopital Nord-CHU St Etienne
city: Toulouse
country: France
facility: Hôpital des enfants
city: Tours
country: France
facility: Hôpital Clocheville
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Hamburg
country: Germany
facility: Kinderkrankenhaus Wilhelmstift
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Kinderchirurgische Klinik Ludwig-Maximilians-Universität
city: Budapest
country: Hungary
facility: Heim Pál Gyermekkórház,
city: Bari
country: Italy
facility: University of Bari
city: Milano
country: Italy
facility: Clinica Dermatologica
city: Vilnius
country: Lithuania
facility: Vilnius University Children's Hospital
city: Mexico CIty
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez
city: Auckland
country: New Zealand
facility: Auckland Dermatology
city: Hamilton
country: New Zealand
facility: Waikato Clinical Research 2008 Ltd.
city: Lima
country: Peru
facility: Clinica Internacional
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins
city: Lima
country: Peru
facility: Instituto Nacional de Salud del Niño
city: Gdansk
country: Poland
facility: Klinika Chirurgii i Urologii Dzieci i Mlodziezy Akademii Medycznej
city: Krakow
country: Poland
facility: University Children's Hospital
city: Lodz
country: Poland
facility: Department of Pediatric Surgery and Oncology
city: Warszawa
country: Poland
facility: Klinika Onkologii, Centrum Zdrowia Dziecka
city: Bucharest
country: Romania
facility: Spitalul Clinic Urgenta pentru Copii Grigore Alexandrescu
city: Bucharest
country: Romania
facility: I.O.M.C Alfred Rusescu
city: Bucharest
country: Romania
facility: Spitalul de Copii Dr. Victor Gomoiu
city: Iasi
country: Romania
facility: Spitalul Clinic de Urgenta pentu Copii Sf. Maria
city: Timisoara
country: Romania
facility: Spitalul de Urgenta Copii, Louis Turcanu
city: Moscow
country: Russian Federation
facility: Medical University - Filatov Pediatric Hospital
city: St-Peterburg
country: Russian Federation
facility: Medical Pediatric Academy
city: St-Peterburg
country: Russian Federation
facility: Neonatal Intensive Care Department
city: A Coruna
country: Spain
facility: Servicio de Dermatologia del Hospital Infantil
city: Barcelona
country: Spain
facility: Hospital Sant Pau de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Infantil Niño Jesús
city: Madrid
country: Spain
facility: Hospital La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario de Valencia
Study officials:
affiliation: Hopital de Bordeaux
name: Christine Labreze, MD
role: STUDY_CHAIR
References:
citation: Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.
citation: Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, Lipsker D, Dupuis E, Ezzedine K, Vergnes P, Taieb A, Leaute-Labreze 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.
citation: Leaute-Labreze 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, Febrer Bosch MI, Su J, Buckova H, Torrelo A, Cambazard F, Grantzow R, Wargon O, Wyrzykowski D, Roessler J, Bernabeu-Wittel J, Valencia AM, Przewratil P, Glick S, Pope E, Birchall N, Benjamin L, Mancini AJ, Vabres P, Souteyrand P, Frieden IJ, Berul CI, Mehta CR, Prey S, Boralevi F, Morgan CC, Heritier S, Delarue A, Voisard JJ. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 2015 Feb 19;372(8):735-46. doi: 10.1056/NEJMoa1404710.