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Open Access 01-12-2024 | Allopurinol | Update

Detailed statistical analysis plan for ALBINO: 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)

Authors: Corinna Engel, Mario Rüdiger, Manon J. N. L. Benders, Frank van Bel, Karel Allegaert, Gunnar Naulaers, Dirk Bassler, Katrin Klebermaß-Schrehof, Maximo Vento, Ana Vilan, Mari Falck, Isabella Mauro, Marjo Metsäranta, Sampsa Vanhatalo, Jan Mazela, Tuuli Metsvaht, Roselinda van der Vlught, Axel R. Franz, for the ALBINO Study Group

Published in: Trials | Issue 1/2024

Abstract

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.

Available only for authorised users

Paper version of PARCA-R questionnaire will be filled by parents and inserted into the eCRF by the staff of each center.

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Title: Detailed statistical analysis plan for ALBINO: 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)
Authors: Corinna Engel
Mario Rüdiger
Manon J. N. L. Benders
Frank van Bel
Karel Allegaert
Gunnar Naulaers
Dirk Bassler
Katrin Klebermaß-Schrehof
Maximo Vento
Ana Vilan
Mari Falck
Isabella Mauro
Marjo Metsäranta
Sampsa Vanhatalo
Jan Mazela
Tuuli Metsvaht
Roselinda van der Vlught
Axel R. Franz
for the ALBINO Study Group
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Allopurinol
Perinatal Asphyxia
Encephalopathy
Published in: Trials / Issue 1/2024
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-023-07828-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Detailed statistical analysis plan for ALBINO: 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)

Abstract

Background

Methods/design

Results

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods/design

Results

Discussion

Trial registration

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