Perinatal Asphyxia, hypoxic-ischemic brain injury MedDRA version: 20.0 Level: PT Classification code 10028923 Term: Neonatal asphyxia System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level: PT Classification code 10014633 Term: Encephalopathy neonatal System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: ACEPURIN
Product Name: Allokid
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Allopurinol sodium
CAS Number: 17795-21-0
Other descriptive name: ALLOPURINOL SOD
Sponsors
University Hospital Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Term and near-term infants with a history of disturbed labour who meet at least one sign of perinatal asphyxia and early clinical signs of potentially evolving encephalopathy as defined herein: Perinatal asphyxia: At least 1 out of the following 4criteria must be met - Umbilical (or arterial or reliable venous) blood gas within 30 min after birth with pH=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - gestational age below 36 weeks - birth weight below 2500 g - postnatal age >30min at the end of the screening phase - severe congenital malformation or syndrome requiring neonatal surgery or affecting long-term outcome - patient considered “moribund” or decision for “comfort care only” before study drug administration - parents declined study participation as response to community engagment - both parents are insufficiently fluent in the study site’s national language or English or do not have the intellectual capacity to understand the study procedures and to give consent as judged by the personel who had been in contact with the mother/father before delivery. - both parents/guardians underaged, in case of single parent/guardian this one underaged
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether in newborns with asphyxia and early clinical signs of hypoxic-ischemic encephalopathy, early postnatal allopurinol compared to placebo (mannitol) administered in addition to standard of care (including therapeutic hypothermia if indicated) reduces the incidence of death or severe neurodevelopmental impairment (as defined herein) at 24 months of age. ;Secondary Objective: To evaluate the effect of allopurinol in addition to hypothermia (if indicated) on: - components of the primary outcome variable -brain injury assessed by magnetic resonance imaging, -amplitude integrated electroencephalogram, -full scale electroencephalogram, -laboratory biomarkers and markers of peroxidation - heart function assessed by echocardiography To evaluate the safety of allopurinol in neonates treated with hypothermia. To study pharmacokinetics of allopurinol (verum) and mannitol (placebo) in neonates treated with hypothermia and not treated with hypothermia ;Primary end point(s): Death or severe neurodevelopmental impairment at the age of two years (where severe neurodevelopmental impairment is defined as any of the following: cognitive or language delay defined as mental developmental index (MDI) cognitive or language score on the Bayley Scales of Infant Development (3rd edition) < 85 and/or cerebral palsy according to SCPE criteria [SCPE Dev Med Child Neurol 2000].;Timepoint(s) of evaluation of this end point: at the age of two years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Death or neurodevelopmental impairment (NDI) The primary endpoint will be reconstituted as dichotomised composite secondary endpoint (survival without NDI versus Death or language-composite-score < 85 or cognitive-composite-score <85 or cerebral palsy present). This will be analyzed by Cochrane-Mantel-Haenzel- X²-Test. 2) Incidence of death Incidence of death will be analyzed by Cochrane-Mantel-Haenzel- X²-Test. 3) Incidence of CP Incidence of CP will be analyzed by Cochrane-Mantel-Haenzel- X²-Test. 4) 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. Analysis will be done by using Wilcoxon-Mann-Whitney test. 5) Motor-Composite-Score (Bayley III) The nummerical data of the motor-composite-score will be analysed using Wilcoxon-Mann-Whitney test. The use of this test accounts for the fact that data will be cut due to lack sensitivity below 50 points. 6) Motor-Composite-Score dichotomised (Bayley III) The motor-composite-score will be dichotomised at the cut-off <85 versus =85 and analysed by Cochrane-Mantel-Haenzel- X²-Test. 7) Cognitive-Composite-Score (cognitive subscale, Bayley III) The nummerical data of the cognitive-composite-score will be analysed using Wilcoxon-Mann-Whitney test. The use of this test accounts for the fact that data will be cut due to lack sensitivity below 50 points. 8) Cognitive-Composite-Score dichotomised (cognitive subscale, Bayley III) The cognitive-composite-score will be dichotomised at the cut-off <85 versus =85 and analysed by Cochrane-Mantel-Haenzel- X²-Test. 9) Language-Composite-Score (language subscale, Bayley III) The raw nummerical data of the language-composite-score will be analysed using Wilcoxon-Mann-Whitney test. The use of this test accounts | — |
Countries
Austria, Belgium, Estonia, Finland, Germany, Italy, Netherlands, Norway, Portugal, Spain, Switzerland
Contacts
Public ContactClinical Trial Center
Center for Pediatric Clinical Studies
Outcome results
None listed