TY - JOUR
T1 - Detailed statistical analysis plan for ALBINO
T2 - 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)
AU - Engel, Corinna
AU - Rüdiger, Mario
AU - Benders, Manon J N L
AU - van Bel, Frank
AU - Allegaert, Karel
AU - Naulaers, Gunnar
AU - Bassler, Dirk
AU - Klebermaß-Schrehof, Katrin
AU - Vento, Maximo
AU - Vilan, Ana
AU - Falck, Mari
AU - Mauro, Isabella
AU - Metsäranta, Marjo
AU - Vanhatalo, Sampsa
AU - Mazela, Jan
AU - Metsvaht, Tuuli
AU - van der Vlught, Roselinda
AU - Franz, Axel R
N1 - Publisher Copyright:
© 2024, The Author(s).
PY - 2024/1/24
Y1 - 2024/1/24
N2 - BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE.METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years.RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups.DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.
AB - BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE.METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years.RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups.DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.
KW - Allopurinol
KW - Brain injury
KW - Cerebral palsy
KW - Childbirth outcome
KW - Hypothermia therapy
KW - Hypoxic-ischemic encephalopathy
KW - Neonatal oxygen deficiency
KW - Perinatal asphyxia
UR - http://www.scopus.com/inward/record.url?scp=85183028680&partnerID=8YFLogxK
U2 - 10.1186/s13063-023-07828-6
DO - 10.1186/s13063-023-07828-6
M3 - Article
C2 - 38267942
SN - 1745-6215
VL - 25
JO - Trials
JF - Trials
IS - 1
M1 - 81
ER -