ACUMEN: Acute High Dose Melatonin for Encephalopathy of the Newborn

You may be able to join if

• Baby admitted to the Neonatal Intensive Care Unit (NICU) with moderate-severe hypoxic-ischaemic encephalopathy (HIE) meeting eligibility criteria for therapeutic hypothermia (HT) (in accordance with local guidelines) and: a) Born at ≥36 completed weeks gestation; b) Clinically stable* at the time of IMP administration; c)Invasive blood pressure monitoring in situ prior the administration of the IMP loading dose.
• All participants will undergo a further assessment of HIE grade as determined by amplitude-integrated EEG (aEEG)/EEG and/or a Modified Sarnat neurological examination prior to IMP administration: a) Sentinel Participant Criteria Only: must not meet the criteria for severe HIE.
• Informed consent from parents/guardians/person with legal responsibility.
• Definition of Clinical Stability Eligibility of the participant must be rechecked prior to administration of the IMP given the varying clinical status of these infants. Stability will take the following into consideration: 1. Well placed central venous catheter or patent peripheral cannula in situ. 2. Haemodynamic stability within 30 minutes prior to IMP administration: a. Mean blood pressure (without inotropic support) must be greater than the 5th centile for gestation (see BP centile charts in Appendix 3) prior to administration of the loading dose. b. Mean blood pressure (with or without inotropic support) must be greater than the 5th centile for gestation (see BP centile charts in Appendix 3) prior to administration of each maintenance dose. i. The participant must not be receiving more than one vasoactive inotrope. ii. The Vasoactive-Inotropic Score (VIS) must be ≤10. The VIS score is calculated as: VIS = dopamine (μg/kg/min) + dobutamine (μg/kg/min) + [100 x adrenaline (μg/kg/min)] + [100 x noradrenaline (μg/kg/min)] 3. No evidence of acute kidney injury resulting in hyperkalaemia (defined as a serum potassium >6.5mmol/L) that continues to rise despite stopping potassium containing infusions and potassium sparing drugs (based on the most recent available blood test result). 4. No clinical concerns of acute liver failure for the loading dose†. 5. No evidence of ongoing acute liver failure defined as INR >3 (despite administration of parenteral vitamin K or clotting factor replacement) for administration of maintenance doses based on the most recent blood test. 6. Clinical or electrographic seizures, if present, controlled with anti-seizure medications. If there are seizures, these must not be ongoing or uncontrolled despite anti-seizure medications. 7. Clinical observations within acceptable range for an infant undergoing therapeutic hypothermia. 8. No clinical stability concerns from the attending neonatologist.