Clinical trial • Phase III • Neurology|Rare Disease
Allopurinol sodium for Hypoxic-ischemic encephalopathy (HIE)|Neonatal asphyxia
Phase III trial of Allopurinol sodium for Hypoxic-ischemic encephalopathy (HIE)|Neonatal asphyxia.
Overview
- Trial Therapeutic Area
- Neurology|Rare Disease
- Trial Disease
- Hypoxic-ischemic encephalopathy (HIE)|Neonatal asphyxia
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 06-08-2024
- First CTIS Authorization Date
- 10-09-2024
Trial design
Randomised, placebo arm: mannitol (solution for infusion) administered iv as placebo; allopurinol (acepurin) investigational arm administered iv (active substance: allopurinol sodium). dosing unit information present (mg/kg) with max daily dose amount 30 mg/kg; study is placebo-controlled and compares allopurinol plus standard of care versus placebo plus standard of care (standard care may include therapeutic hypothermia if indicated). Phase III trial across 36 sites in Germany, Italy, Norway and others.
- Randomised
- Yes
- Comparator
- Placebo arm: MANNITOL (solution for infusion) administered IV as placebo; Allopurinol (ACEPURIN) investigational arm administered IV (active substance: allopurinol sodium). Dosing unit information present (mg/kg) with max daily dose amount 30 mg/kg; study is placebo-controlled and compares allopurinol plus standard of care versus placebo plus standard of care (standard care may include therapeutic hypothermia if indicated).
- Trial Duration For Participant
- 730
Eligibility
Recruits 452 paediatric patients.
- Vulnerable Population
- Neonates (newborns) are a vulnerable population; consent is obtained from parents/legal guardians. Subject information and informed consent forms for parents/guardians are provided (country-specific documents listed in multiple languages). Assent is not applicable for neonates.
Inclusion criteria
- {"criterion_text":"- Severe perinatal metabolic acidosis or ongoing cardiopulmonary resuscitation at 5 min after birth\n- Early clinical signs of potentially evolving encephalopathy"}
Exclusion criteria
- {"criterion_text":"- gestational age below 36 weeks\n- birth weight below 2500 g\n- postnatal age >30min at the end of screening phase\n- severe congenital malformation or syndrome requiring neonatal surgery or affecting long-term outcome\n- patient considered “moribund” / “non-viable” (e.g., lack of spontaneous cardiac activity and ongoing chest compression at 30min)"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Death versus severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years","definition_or_measurement_approach":"Severe neurodevelopmental impairment defined as cerebral palsy, or cognitive or language impairment (cognitive- and language-composite scores of the Bayley Scales of Infant and Toddler Development, 3rd edition <85) assessed at 24 months of age."}
Secondary endpoints
- {"endpoint_text":"- Death or neurodevelopmental impairment (NDI) The primary endpoint will be reconstituted as dichotomised composite secondary endpoint (survival without NDI versus Death or languagecomposite- score < 85 or cognitive-composite-score <85 or cerebral palsy present).","definition_or_measurement_approach":"Dichotomised composite: survival without NDI versus death or Bayley language-composite <85 or cognitive-composite <85 or presence of cerebral palsy."}
- {"endpoint_text":"- Incidence of CP Incidence of CP will be analyzed by Cochrane-Mantel-Haenzel- X²-Test.","definition_or_measurement_approach":"Incidence of cerebral palsy analyzed using Cochrane-Mantel-Haenszel chi-square test."}
- {"endpoint_text":"- GMFCS-score GMFCS-Score for quantification of the effects of cerebral palsy and other motor impairments (adapted from Palisano et al. [Palisano Med Child Neurol 1997]) using the ALBINO-GMFCS-score sheet (separate document not part of this protocol) will be analysed. GMFCS-score consists of six categories.","definition_or_measurement_approach":"Gross Motor Function Classification System (GMFCS) categories (six categories) assessed using ALBINO-GMFCS-score sheet."}
- {"endpoint_text":"- Motor-Composite-Score (Bayley III)","definition_or_measurement_approach":"Motor composite score from Bayley Scales of Infant and Toddler Development, 3rd edition."}
- {"endpoint_text":"- Motor-Composite-Score dichotomised (Bayley III) The motor-composite-score will be dichotomised at the cut-off <85 versus ≥85","definition_or_measurement_approach":"Motor-composite score dichotomised at <85 versus ≥85."}
- {"endpoint_text":"- Cognitive-Composite-Score (cognitive subscale, Bayley III)","definition_or_measurement_approach":"Cognitive composite score from Bayley III cognitive subscale."}
- {"endpoint_text":"- Cognitive-Composite-Score dichotomised (cognitive subscale, Bayley III) The cognitive-composite-score will be dichotomised at the cut-off <85 versus ≥85","definition_or_measurement_approach":"Cognitive-composite score dichotomised at <85 versus ≥85."}
- {"endpoint_text":"- Language-Composite-Score (language subscale, Bayley III)","definition_or_measurement_approach":"Language composite score from Bayley III language subscale."}
- {"endpoint_text":"- Language-Composite-Score dichotomised (language subscale, Bayley III) The language-composite-score will be dichotomised at the cut-off <85 versus ≥85","definition_or_measurement_approach":"Language-composite score dichotomised at <85 versus ≥85."}
- {"endpoint_text":"- Single Components of primary endpoint - Graph Single components and observed combinations of the primary endpoint (healthy, death, CP, language-composite-score <85, cognitive-composite- score <85) will be displayed graphically stratified for the two treatment groups.","definition_or_measurement_approach":"Graphical display of individual components and observed combinations of primary endpoint stratified by treatment group."}
Recruitment
- Recruitment Window Months
- 99
- Consent Approach
- Informed consent is provided by parents/legal guardians (parents and guardians ICFs available). Subject information and informed consent forms for parents/guardians are provided as country-specific documents; available languages/country documents include (examples in documents list) English, Dutch, German, French, Spanish, Finnish, Russian, Italian and country-specific translations. Assent is not applicable for neonates.
Geography
- Total Number Of Sites
- 36
- Total Number Of Participants
- 452
Germany
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 14-01-2025
- Processing Time Days
- 145
- Number Of Sites
- 8
- Number Of Participants
- 112
Sites
- Site Name
- Universitaetsklinikum Muenster AöR
- Department Name
- Neonatology
- Contact Person Name
- Jenny Potratz
- Contact Person Email
- jenny.potratz@ukmuenster.de
- Site Name
- Universitaet Leipzig
- Department Name
- Neonatology
- Contact Person Name
- Ulrich Thome
- Contact Person Email
- ulrich.thome@medizin.uni-leipzig.de
- Site Name
- Universitaetsklinikum Duesseldorf AöR
- Department Name
- Neonatology
- Contact Person Name
- Thomas Hoehn
- Contact Person Email
- thomas.hoehn@uni-duesseldorf.de
- Site Name
- Cnopf'sche Kinderklinik/Klinik Hallerwiese
- Department Name
- Neonatology
- Contact Person Name
- Michael Schroth
- Contact Person Email
- michael.schroth@diakoneo.de
- Site Name
- Auf der Bult Kinder- und Jugendkrankenhaus
- Department Name
- Neonatology
- Contact Person Name
- Anna Koluch
- Contact Person Email
- koluch@hka.de
- Site Name
- University Of Tuebingen
- Department Name
- Neonatology
- Contact Person Name
- Axel Franz
- Contact Person Email
- axel.franz@med.uni-tuebingen.de
- Site Name
- KJF Klinik Josefinum, Klinik für Kinder und Jugendliche
- Department Name
- Neonatology
- Contact Person Name
- Thomas Völkl
- Contact Person Email
- voelkl.thomas@josefinum.de
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
- Department Name
- Neonatology
- Contact Person Name
- Barbara Seipolt
- Contact Person Email
- Barbara.Seipolt@uniklinikum-dresden.de
Italy
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 20-05-2025
- Processing Time Days
- 271
- Number Of Sites
- 3
- Number Of Participants
- 23
Sites
- Site Name
- ASST FBF-Sacco Ospedale dei Bambini "V.Buzzi"
- Department Name
- Neonatology
- Contact Person Name
- Gianluca Lista
- Contact Person Email
- gianluca.lista@asst-fbf-sacco.it
- Site Name
- Azienda Sanitaria Universitaria Friuli Centrale (ASUFC)
- Department Name
- Neonatology
- Contact Person Name
- Isabella Mauro
- Contact Person Email
- isabella.mauro@asufc.sanita.fvg.it
- Site Name
- Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi
- Department Name
- Neonatology
- Contact Person Name
- Virgilio Carnielli
- Contact Person Email
- v.carnielli@staff.univpm.it
Norway
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 10-09-2024
- Processing Time Days
- 19
- Number Of Sites
- 1
- Number Of Participants
- 36
Sites
- Site Name
- Oslo Universitetssykehus UUS
- Department Name
- Neonatology
- Contact Person Name
- Mari Falck
- Contact Person Email
- mfalck@ous-hf.no
Spain
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 06-08-2025
- Processing Time Days
- 349
- Number Of Sites
- 2
- Number Of Participants
- 32
Sites
- Site Name
- Hospital Universitario La Fe
- Department Name
- Neonatology
- Contact Person Name
- Maximo Vento
- Contact Person Email
- maximo.vento@uv.es
- Site Name
- Hospital General Alicante
- Department Name
- Neonatology
- Contact Person Name
- Caridad Tapia Collados
- Contact Person Email
- ctapiac@coma.es
Finland
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 12-09-2024
- Processing Time Days
- 21
- Number Of Sites
- 2
- Number Of Participants
- 67
Sites
- Site Name
- Helsingin ja Uudenmaan Sairaanhoitopiirin Kuntayhtämy (HUS)
- Department Name
- Neonatology
- Contact Person Name
- Marjo Metsäranta
- Contact Person Email
- marjo.metsaranta@hus.fi
- Site Name
- Jorvi Hospital, HUS
- Department Name
- Neonatology
- Contact Person Name
- Marjo Metsäranta
- Contact Person Email
- marjo.metsaranta@hus.fi
Netherlands
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 06-08-2025
- Processing Time Days
- 349
- Number Of Sites
- 13
- Number Of Participants
- 90
Sites
- Site Name
- St. Antonius Ziekenhuis
- Department Name
- Neonatology
- Contact Person Name
- Jacqueline van Hillegersberg
- Contact Person Email
- j.hillegersberg@antoniusziekenhuis.nl
- Site Name
- Deventer Ziekenhuis
- Department Name
- Neonatology
- Contact Person Name
- Anne Dassel
- Contact Person Email
- c.dassel@dz.nl
- Site Name
- Maxima Medisch Centrum
- Department Name
- Neonatology
- Contact Person Name
- Koenraad Dijkman
- Contact Person Email
- k.dijkman@mmc.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Neonatology
- Contact Person Name
- Frank van Bel
- Contact Person Email
- f.vanbel@umcutrecht.nl
- Site Name
- Isala Kliniek Zwolle
- Department Name
- Neonatology
- Contact Person Name
- Marianne van der Heide
- Contact Person Email
- m.jalving@isala.nl
- Site Name
- Diakonessenhuis Stichting
- Department Name
- Neonatology
- Contact Person Name
- Inge de Boer
- Contact Person Email
- idboer@diakhuis.nl
- Site Name
- Sint Elisabeth Ziekenhuis Tilburg
- Department Name
- Neonatology
- Contact Person Name
- Carien Smeets
- Contact Person Email
- c.smeets@elisabeth.nl
- Site Name
- Spaarne Gasthuis
- Department Name
- Neonatology
- Contact Person Name
- Marianne van Houten
- Contact Person Email
- mvanhouten@spaarneziekenhuis.nl
- Site Name
- Vumc Medical Center - Emma's Children's Hospital
- Department Name
- Neonatology
- Contact Person Name
- Mirjam van Weissenbruch
- Contact Person Email
- m.vanweissenbruch@vumc.nl
- Site Name
- Meander Medisch Centrum
- Department Name
- Neonatology
- Contact Person Name
- Clemens Meijssen
- Contact Person Email
- cb.meijssen@meandermc.nl
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Neonatology
- Contact Person Name
- Gerbrich van den Bosch
- Contact Person Email
- g.vandenbosch@erasmusmc.n
- Site Name
- OLVG
- Department Name
- Neonatology
- Contact Person Name
- Sophie van der Schoor
- Contact Person Email
- s.r.d.vanderschoor@olvg.nl
- Site Name
- Albert Schweitzer Ziekenhuis
- Department Name
- Neontatology
- Contact Person Name
- Miranda de Jong
- Contact Person Email
- m.dejong@asz.nl
Austria
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 14-01-2025
- Processing Time Days
- 145
- Number Of Sites
- 3
- Number Of Participants
- 49
Sites
- Site Name
- Universitätsklinik für Kinder- und Jugendheilkunde
- Department Name
- Klinische Abteilung für Neonatologie
- Contact Person Name
- Gerhard Pichler
- Contact Person Email
- gerhard.pichler@medunigraz.at
- Site Name
- Medizinische Universität Wien
- Department Name
- Klinische Abteilung für Neonatologie, Pädiatrische Intensivmedizin und Neuropädiatrie
- Contact Person Name
- Katrin Klebermass-Schehof
- Contact Person Email
- katrin.klebermass-schrehof@meduniwien.ac.at
- Site Name
- Universitätsklinik für Kinder- und Jugendheilkunde der PMU
- Department Name
- Division für Neonatologie
- Contact Person Name
- Martin Wald
- Contact Person Email
- neooffice@salk.at
Estonia
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 16-09-2024
- Processing Time Days
- 25
- Number Of Sites
- 2
- Number Of Participants
- 14
Sites
- Site Name
- Tartu University Hospital
- Department Name
- Neonatology
- Contact Person Name
- Tuuli Metsvaht
- Contact Person Email
- tuuli.metsvaht@kliinikum.ee
- Site Name
- East Tallinn Central Hospital
- Department Name
- Neonatology
- Contact Person Name
- Pille Andresson
- Contact Person Email
- pille.andresson@itk.ee
Belgium
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 06-08-2025
- Processing Time Days
- 349
- Number Of Sites
- 2
- Number Of Participants
- 29
Sites
- Site Name
- CHR de la Citadelle
- Department Name
- Neonatology
- Contact Person Name
- Renaud Viellevoye
- Contact Person Email
- renaud.viellevoye@chrcitadelle.be
- Site Name
- KU Leuven
- Department Name
- Neonatology
- Contact Person Name
- Gunnar Naulaers
- Contact Person Email
- gunnar.naulaers@uzleuven.be
Sponsor
Primary sponsor
- Full Name
- Universitaetsklinikum Tuebingen AöR
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Germany
Investigational products
- Investigational Product Name
- ACEPURIN, poeder voor infusievloeistof 1g/100 ml
- Active Substance
- Allopurinol sodium
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- Authorised (marketing authorisation RVG 09974 in NL)
- Orphan Designation
- Yes
- Maximum Dose
- 30 mg/kg
- Investigational Product Name
- MANNITOL
- Active Substance
- Mannitol
- Modality
- Small molecule
- Routes Of Administration
- SOLUTION FOR INFUSION
- Route
- Infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 30 mg/kg
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