TREATMENT OF HYPOTENSION IN EXTREMELY PRETERM INFANTS: A MULTICENTER RANDOMIZED CONTROLLED TRIAL

INTERVENTION: Pharmaceutical Form: Solution for injection INN or Proposed INN: Dopamine Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical Form: Solution for injection INN or Proposed INN: Dobutamine Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Pharmaceutical Form: Solution for injection INN or Proposed INN: Epinephrine Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1‐ Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: Hydrocortisone Concentration type: equal CONDITION: HYPOTENSION IN EXTREMELY PRETERM INFANTS ; MedDRA version: 9.1 Level: LLT Classification code 10049223 ; MedDRA version: 9.1 Level: LLT Classification code 10049223 ; MedDRA version: 9.1 Level: LLT Classification code 10049223 ; MedDRA version: 9.1 Level: LLT Classification code 10049223 PRIMARY OUTCOME: Main Objective: The primary outcome will be comparing, in terms of clinically relevant outcomes ( the combined end point of mortality or a severe neurological damage (severe IVH at day 7 or cystic PVL at day 28 or discharge, the policy of immediately treating extremely preterm neonates with hypotension starting with dopamine, with the policy of treating only those who also present clinical or ultrasound signs of low perfusion, starting with dobutamine. Primary end point(s): The primary outcome will be the combined end point of mortality or a severe neurological outcome [severe intraventricular hemorrhage or cystic periventricular leucomalacia]. Secondary Objective: Secondary outcomes will be the estimation, in the 2 groups, of the frequency of: Necrotizing enterocolitis Retinopathy of prematurity Bronchopulmonary displasia Renal impairment and hyperkalemia Other adverse events that could be caused by treatments (eg, arrhythmia, hypertension, seizures, thyroid hormonal effects) On a non‐randomized subsample: measures of organ perfusion (eg, superior vena cava flow, pulmonary artery flow at ultrasound (US); right ventricular output; cardiovascular score), and relationship between BP and perfusion indices, and between US and clinical indices of perfusion. INCLUSION CRITERIA: premature neonates 23‐30 weeks gestation that present hypotension (BP < threshold for at least 10 minutes), and whose parents have given an informed consent to the study. The BP threshold for inclusion is based on GA (Attachment 1). Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range