Data di registrazione della sperimentazione
30 gen 2017
Inserimento del primo partecipante
2 ago 2017
Stato di reclutamento
Not Recruiting
Titolo scientifico
(Fonte di dati: WHO)
Effect of ALlopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome ? a blinded randomized placebo-controlled parallel group multicenter trial for superiority (Phase III) - ALBINO
Tipo di sperimentazione
(Fonte di dati: WHO)
Interventional clinical trial of medicinal product
Disegno della sperimentazione
(Fonte di dati: WHO)
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: multicenter trial If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
Fase
(Fonte di dati: WHO)
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
Punti finali primari
(Fonte di dati: WHO)
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
Punti finali secondari
(Fonte di dati: WHO)
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- X?-Test.
2) Incidence of death
Incidence of death will be analyzed by Cochrane-Mantel-Haenzel- X?-Test.
3)Incidence of CP
Incidence of CP will be analyzed by Cochrane-Mantel-Haenzel- X?-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- X?-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- X?-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 for the fact that data will be cut due to lack sensitivity below 50 points.
10)Language-Composite-Score dichotomised (language subscale, Bayley III)
The language-composite-score will be dichotomised at the cut-off <85 versus =85 and analysed by Cochrane-Mantel-Haenzel- X?-Test.
11)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.
;Timepoint(s) of evaluation of this end point: Secondary endpoints will be analysed at 24 months corrected age between the two treatment groups.
Contatto per informazioni
(Fonte di dati: WHO)
European Union
