Effect of Allopurinol for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome

• Register: ClinicalTrials.gov
• Last refreshed on: 18 July 2023
• Main ID: NCT03162653
• Date of registration: 18/05/2017
• Prospective Registration: Yes
• Primary sponsor: University Hospital Tuebingen
• Public title: Effect of Allopurinol for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome ALBINO
• Scientific title: 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)
• Date of first enrolment: March 25, 2018
• Target sample size: 760
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03162653
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Estonia, Finland, Germany, Italy, Netherlands, Norway, Poland, Portugal, Spain, Switzerland

Contacts

• Name: Oldershausen Gabriele

• Name: Rüdiger Mario, Prof. Dr.
• Affiliation: University Children's Hospital Dresden

• Name: Axel Franz, Prof. Dr.
• Affiliation: University Children's Hospital Tuebingen

Key inclusion & exclusion criteria

Inclusion criteria

Term and near-term infants with a history of disturbed labour who meet at least one
criterion of perinatal acidosis (or ongoing resuscitation) and at least two early clinical
signs of potentially evolving encephalopathy as defined herein:

Severe perinatal metabolic acidosis or ongoing cardiopulmonary resuscitation at 5 min after
birth:

At least 1 out of the following 5 criteria must be met

- Umbilical (or arterial or reliable venous) blood gas within 30 min after birth with
pH<7.0

- Umbilical (or arterial or reliable venous) blood gas within 30 min after birth with
base deficit =16 mmol/l

- Need for ongoing cardiac massage at/beyond 5 min postnatally

- Need for adrenalin administration during resuscitation

- APGAR score =5 at 10min AND

Early clinical signs of potentially evolving encephalopathy:

At least 2 out of the following 4 criteria must be met:

- Altered state of consciousness (reduced or absent response to stimulation or
hyperexcitability)

- Severe muscular hypotonia or hypertonia,

- Absent or insufficient spontaneous respiration (e.g., gasping only) with need for
respiratory support at 10 min postnatally

- Abnormal primitive reflexes (absent suck or gag or corneal or Moro reflex) or abnormal
movements (e.g., potential clinical correlates of seizure activity)

Exclusion criteria

- gestational age below 36 weeks

- birth weight below 2500 g

- postnatal age >30min at the end of screening phase

- severe congenital malformation or syndrome requiring neonatal surgery or affecting
long-term outcome

- patient considered "moribund" / "non-viable" (e.g., lack of spontaneous cardiac
activity and ongoing chest compression at 30min)

- decision for "comfort care only" before study drug administration

- parents declined study participation as response to measures of community engagement

- both parents are insufficiently fluent in the study site's national language(s) or
English or do not seem to have the intellectual capacity to understand the study
procedures and to give consent as judged by the personnel who had been in contact with
the mother/father before delivery.

- both parents/guardians less than 18 years of age, in case of single parent/guardian
this one less than 18 years of age



Age minimum: N/A
Age maximum: 45 Minutes
Gender: All

Health Condition(s) or Problem(s) studied

Encephalopathy, Hypoxic-Ischemic

Infant, Newborn, Diseases

Intervention(s)

Drug: Mannitol

Drug: Allopurinol

Primary Outcome(s)

death versus severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment [Time Frame: at the age of 24 months]

Secondary Outcome(s)

GMFCS-score [Time Frame: at 24 months]

Incidence of CP [Time Frame: at 24 months]

Language-Composite-Score dichotomised (language subscale, Bayley III) [Time Frame: at 24 months]

Incidence of Death [Time Frame: at 24 months]

Language-Composite-Score (language subscale, Bayley III) [Time Frame: at 24 months]

Cognitive-Composite-Score dichotomised (cognitive subscale, Bayley III) [Time Frame: at 24 months]

Cognitive-Composite-Score (cognitive subscale, Bayley III) [Time Frame: at 24 months]

Death or neurodevelopmental impairment (NDI) [Time Frame: at 24months]

Motor-Composite-Score dichotomised (Bayley III) [Time Frame: at 24 months]

Motor-Composite-Score (Bayley III) [Time Frame: at 24 months]

Secondary ID(s)

ALBINO

2016-000222-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Fundación para la Investigación del Hospital Clínico de Valencia

ACE Pharmaceuticals BV

Helsingin Ja Uudenmaan Sairaanhoitopiirin

Oslo University Hospital

Poznan University of Medical Sciences

UMC Utrecht

KU Leuven

Technische Universität Dresden

University of Zurich

Università degli Studi di Udine

University of Helsinki

University of Vienna

Tartu University Hospital

Universidade do Porto