HIP trial - Management of Hypotension In the Preterm Extremely Low Gestational Age Newborn

From 01-07-2011 to 30-10-2017

Description

HYPOTHESIS:A more restricted approach to the management of hypotension in the preterm extremely low gestational age newborninfant (ELGAN) will result in a reduction in the incidence of death or severe cranial ultrasound abnormality at 36weeks gestational age.

PRIMARY OBJECTIVE:To determine whether a more restricted approach to the diagnosis and management of hypotension compared to astandard approach, within the first 72 hrs of life (transitional period), with epinephrine or dopamine as a first lineinotrope, affects survival without significant brain injury at 36 weeks gestational age in infants born less than 28weeks gestation and affects survival without neurodevelopmental disability at 2 years corrected age.

SECONDARY OBJECTIVES:To determine whether a restricted approach to the diagnosis and management of hypotension, with epinephrinecompared to dopamine, affects all cause mortality at 36 weeks gestational age; to determine whether a restrictedapproach, with epinephrine compared to dopamine, affects incidence of grade III-IV intraventricular haemorrhage orperiventricular leukomalacia on cranial ultrasound; to determine whether inotrope use is associated with adversetreatment effects.

RATIONALE:Assuming an annual birth rate of 10.25 births/1,000 population approximately 25,000 Extremely Low Gestational AgeNewborns are born every year in the EU. Conservative figures estimate that approx 12, 500 ELGAN/ yr arehypotensive and receive inotropes. However the total number of preterm infants in published trials comparingmortality rates with various inotropes is only 163 patients. It is therefore essential that we now design and performthe correct trials to determine whether the infusion of inotropic agents is helping or possibly harming these patients.

STUDY DESIGN:Randomised controlled, multi-national clinical trial.

RESEARCH PLAN:Within 3 years 800 infants of 23-28weeks gestational age will be randomised to two alternative pathways todetermine the optimum treatment regime for the management of hypotension in the transitional period (first 72 hrs oflife). Study drugs will be administered until infants are deemed to no longer be hypotensive. The primary outcome ofsurvival without brain injury will be determined at 36 weeks corrected gestational age and the co primary outcome ofsurvival without neurodevelopmental disability will be assessed at a corrected age of 24 months. This will be thelargest European trial in the ELGAN.

CLINICAL SIGNIFICANCE:Hypotension is not only associated with mortality of preterm infants but is also associated with brain injury andimpaired neurosensory development in ELGAN survivors. There is a paucity of data to support the current approachto this problem. Preterm brain injury has far reaching implications for the child, parents, family, the health service andsociety at large. It is essential that appropriately designed trials are now performed to address this critical question.

Team

• Sabine Van Huffel, Co-promoter
• Gunnar Naulaers, Promoter (External)
• Alexander Caicedo Dorado, Team member

Financing

Funding: EU Funding - European Funding

Program/Grant Type: EU Other - Other