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Clinical Trial
. 2024 Jan 24;25(1):81.
doi: 10.1186/s13063-023-07828-6.

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)

Corinna Engel  1 , Mario Rüdiger  2 , Manon J N L Benders  3 , Frank van Bel  3 , Karel Allegaert  4 , Gunnar Naulaers  4 , Dirk Bassler  5 , Katrin Klebermaß-Schrehof  6 , Maximo Vento  7 , Ana Vilan  8 , Mari Falck  9 , Isabella Mauro  10 , Marjo Metsäranta  11 , Sampsa Vanhatalo  11 , Jan Mazela  12 , Tuuli Metsvaht  13 , Roselinda van der Vlught  14 , Axel R Franz  15   16 ; ALBINO Study Group
Collaborators, Affiliations
Clinical Trial

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)

Corinna Engel et al. Trials. .

Erratum in

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.

Keywords: Allopurinol; Brain injury; Cerebral palsy; Childbirth outcome; Hypothermia therapy; Hypoxic-ischemic encephalopathy; Neonatal oxygen deficiency; Perinatal asphyxia.

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Conflict of interest statement

R. van der Vlught-Meijer is an employee of ACE Pharmaceuticals, the company that holds the Dutch marketing authorization registration for Acepurin® (allopurinol 1 g/100 ml) for intravenous application for the treatment of gout. C. van Veldhuizen and B. Laméris are the former owners of ACE Pharmaceuticals. All three contributed to the development of the study protocol and therefore the statistical analysis plan. All other contributors declare that they do not have competing interests.

Figures

Fig. 1
Fig. 1
Definition of primary endpoint. If data are not available for the first level of definition, the second level applies, and so on. NDI, neurodevelopmental impairment
See this image and copyright information in PMC

References

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