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)

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • University of Tübingen
  • Utrecht University
  • KU Leuven
  • University of Zurich
  • University of Vienna
  • Hospital Universitario La Fe
  • Centro Hospitalar São João
  • University of Oslo
  • Azienda Sanitaria Universitaria Integrata di Udine
  • University of Helsinki
  • University of Medical Sciences Poznan
  • University of Tartu
  • Ace Pharmaceuticals BV
  • University Hospital Tübingen
  • Vestfold Hospital Trust

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.

Details

Original languageEnglish
Article number81
JournalTrials
Volume25
Issue number1
Publication statusPublished - 24 Jan 2024
Peer-reviewedYes

External IDs

PubMed 38267942

Keywords

Sustainable Development Goals

Keywords

  • Allopurinol, Brain injury, Cerebral palsy, Childbirth outcome, Hypothermia therapy, Hypoxic-ischemic encephalopathy, Neonatal oxygen deficiency, Perinatal asphyxia, Humans, Hypoxia-Ischemia, Brain/diagnosis, Infant, Control Groups, Allopurinol/adverse effects, Brain Injuries, Child, Infant, Newborn, Hypothermia, Induced/adverse effects