A brief summary of HIP

The HIP Trial addresses the FP7 Health call 'Adapting off-patent medicines to the specific needs of paediatric populations' by investigating whether infants born before 28 completed weeks of gestation, a restricted approach to the management of hypotension compared to using dopamine as first line inotrope within the first 72 hrs improves survival without significant brain injury at 36 weeks corrected gestational age and survival without neurodevelopmental disability at 2 years age corrected for prematurity. 

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

There appears to be huge variation in both the diagnosis and treatment of hypotension amongst clinicians. We have previously identified very large variations in practice, both in diagnosing and treating hypotension and we estimate that approximately 12, 5000 ELBW infants annually in the EU receive inotropic support for hypotension. Dopamine is the most commonly used agent, despite there being little evidence to support its use.

Within 3 years up to 830 infants of 23-28 weeks gestational age will be randomised to two alternative pathways to determine the optimum treatment regime for the management of hypotension in the transitional period (first 72 hrs of life). Study drugs will be administered until infants are deemed to no longer be hypotensive. The primary outcome of survival without brain injury will be determined at 36 weeks corrected gestational age and the co primary outcome of survival without neurodevelopmental disability will be assessed at a corrected age of 24 months. This will be the largest European trial in the ELGAN.

Newborn in clinic

By consolidating efforts from basic science, pharmacology and clinical centres, we propose to:

  • Establishing a European-wide, multicentre, randomized, placebo-controlled, double-blind trial to evaluate the efficacy of dopamine for newborns with hypotension.
  • Monitoring long-term outcome in all children studied.
  • Performing pharmacokinetic/ pharmcodynamic studies of dopamine.
  • Developing a dopamine formulation suitable for newborns in order to apply for a Paediatric Use Marketing Authorization (PUMA).