PROVIDE Trial Information

Objective

Preterm birth and being born very small have long-term effects on neurodevelopment and growth. A relatively small percentage of extremely low birthweight (ELBW: birthweight <1000 g) babies suffer from severe neurological disability; however, up to 50% experience some neurodevelopmental or learning impairment in childhood. Current international consensus is that increased protein intake in the neonatal period improves both neurodevelopment and growth, but the quantum of protein required is not known. This trial aims to assess whether providing an extra 1 to 2 g/Kg.d protein in the first 5 days after birth will improve neurodevelopmental outcomes and growth in ELBW babies.

Study Design

Multicentre, double-blind, two-arm, parallel, randomised, controlled trial.

Study Population

Babies born with a birthweight of less than 1000 g in whom an umbilical arterial catheter (UAC) has inserted successfully based on clinical need and whose parents/caregivers have given written informed consent.

Intervention

A Control Group will receive 0.45% saline through the UAC, which is current clinical practice. Babies in the Intervention Group will receive an amino acid solution (TrophAmine) giving an extra 1 g per day of protein above standard intravenous nutrition through the UAC. The intervention will continue for 5 days.

Outcome Measures

Primary study outcome: Survival free from neurodevelopmental disability at 2 years’ corrected age, defined as at least one of: cerebral palsy, blindness, deafness, developmental delay (defined as a standardised score more than 1 SD below the mean (<−1 SD) on the Bayley Scales of Infant Development Edition 3 [Bayley-III] scores), or Gross Motor Function Classification System score[1] ≥1 at 2 years’ corrected gestational age. Secondary outcomes: Growth, from birth to 36 weeks’ corrected gestational age, at NICU discharge and at 2 years’ corrected age; body composition at 36 to 42 weeks’ corrected gestational age measured by air displacement plethysmography and at 2 years’ corrected age; neonatal morbidity, including length of stay; nutritional intake.

Data/Power Analysis

A total of 430 babies (n=215 per group) will provide 85% power at a 5% level of significance (two-sided), to detect an absolute difference of 15% in survival free of neurodevelopmental disability at 2 years’ corrected age, between the two groups (i.e. from 50% to 65%). The sample size has taken into account a 10% loss to follow up rate.

Commencement Date

April 2014

Investigators and Primary Contacts

Principal investigator: Barbara Cormack, BCormack@adhb.govt.nz

Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

Overall Responsible Investigator: Professor Frank Bloomfield, f.bloomfield@auckland.ac.nz

Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

Australia New Zealand Clinical Trials Registry

(ANZCTR) Trial Registry Number: ACTRN12612001084875