Effect of Allopurinol for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO)
Encephalopathy, Hypoxic-Ischemic, Infant, Newborn, Diseases
About this trial
This is an interventional treatment trial for Encephalopathy, Hypoxic-Ischemic focused on measuring Allopurinol, hypothermia therapy, hypoxic-ischemic encephalopathy, neonatal oxygen deficiency, childbirth outcome, perinatal asphyxia
Eligibility 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
Sites / Locations
- Medizinische Universitaet WienRecruiting
- Katholieke Universiteit LeuvenRecruiting
- Tartu UlikoolRecruiting
- Helsingin Ja Uudenmaan Sairaanhoitopiirin KuntayhtymäRecruiting
- University Hospital TübingenRecruiting
- Universita Degli Studi Di UdineRecruiting
- Universitair Medisch Centrum UtrechtRecruiting
- Oslo Universitetssykehus HfRecruiting
- Uniwersytet Medyczny Im Karola Marcinkowskiego W Poznaniu
- Universidade Do Porto
- Para La Investigacion Del Hospital UniversitarioLa Fe De La Comunidad ValencianaRecruiting
- Universitaet ZuerichRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
Allopurinol
Placebo
Allopurinol, powder for injection (PFI), administered in two doses. First dose (20 mg/kg in 2ml/kg sterile water for injection) given as soon as intravenous access is established and no later than 30min postnatally and second dose (10mg/kg in 1ml/kg sterile water for injection) 12 hours thereafter. The second dose will only be administered to in infants on therapeutic hypothermia. Infants who recover quickly and do not qualify for and hence do not undergo hypothermia will not receive a second dose. Administration will be by continuous infusion using a syringe pump over 10min through secure venous access.
mannitol, powder for injection (PFI), administered in two doses. First dose (20 mg/kg in 2ml/kg sterile water for injection) given as soon as intravenous access is established and no later than 30min postnatally and second dose (10mg/kg in 1ml/kg sterile water for injection) 12 hours thereafter. The second dose will only be administered to in infants on therapeutic hypothermia. Infants who recover quickly and do not qualify for and hence do not undergo hypothermia will not receive a second dose. Administration will be by continuous infusion using a syringe pump over 10min through secure venous access.