Impact of the HIP Trial

Impact on the Short and Long Term Health of the most vulnerable neonates

The economic and social cost of brain injury in the preterm infant is considerable as it results in lifelong disability for the child and adult. It is unclear if the current treatment approach actually contributes to brain injury. Therefore, it is essential that we have effective means of diagnosing shock/hypotension in the ELGAN such that only those who require intervention will be treated. The lifelong cost for caring for a child with cerebral palsy/learning difficulties is estimated to be over 2 million euro. This relates to the initial prolonged hospital stay, the costs of recurrent hospitalisations following discharge, and the cost of developmental follow-up does not take into account the huge emotional cost to the family and ultimately society at large.

Conclusive evidence on the safety and efficacy of inotropic drugs for the treatment of hypotension in the ELGAN

This will be the largest study of inotrope use in the ELGAN in the world. This study will be carefully monitored and all clinical data will be carefully examined and recorded. Short-term clinical outcomes will be closely monitored. The efficacy and safety of each treatment will be rigorously assessed. This will include objective assessment of cardiac output with echocardiography, cerebral oxygenation with NIRS and continuous EEG as an indirect measure of cerebral activity. The protocol includes neurodevelopmental follow-up of the cohort of babies at 12 and 24 months. This is one of the strengths of the study and will provide accurate data on the long-term safety of dopamine in Extremely Low Birth Weights (<1000g) (ELBW). This data does not exist and is urgently needed.

Impact on Paediatric Use Marketing Authorisations (PUMA) for newborn babies

This project will develop a PUMA for dopamine for use in the ELGAN. The EU and  the European Parliament and Council Regulation on Medicinal products for Paediatric Use recognises the paucity of data to support many of the medicines used in paediatric practice. The EMEA have provided the framework for PUMA development in the paediatric population. Drugs used in newborn babies, particularly those used for newborn hypotension, have evolved from adult practice and have not been rigorously studied in the ELGAN. This project, through the eventual development of a PUMA, provides the pathway for effecting a real change in clinical practice which should lead to better health outcomes for the truly smallest and most vulnerable members of society.

Economic Impact

This study has the potential not only to significantly improve the health of future generations of European citizens, but also to make a positive impact on expenditure of European health care systems in the future. More immature babies are now surviving as the limits of viability have been continuously reduced such that many babies now delivered at 23 weeks survive. Hypotension is a significant problem in newborns less than 28 weeks and is associated with brain injury. Improved management of this problem will result in a reduction in brain injury with significant short term and long-term health care savings.

The HIP Trial will also promote the activities of two SMEs which are part of the consortium.

  • ClinInfo (France) will develop a web-based randomisation process and databases for data entry throughout the study.
  • BrePco (Ireland) is a pharmaceutical company in the development of medicinal products for paediatric use as well as assistance to research programs for the development, production and regulatory approval in new medicinal products.

Impact on Education

The study will allow young, future European investigators to acquire the core knowledge, skills and attitudes to establish them as new researchers in neonatal care with the subsequent development of research centres in neonatology, particularly the new member states. Most national courses and training initiatives are locally driven, and may not meet rigorous European standards. We plan to focus on a number of areas of education including echocardiography, near infra red spectroscopy, EEG and neurodevelopmental assessment. Experts in each field will coordinate training modules for each enrolled centre. This will have a significant impact on the education and training of clinicians in each centre across Europe and enhance the reputation of Europe as a leader in this area.

Impact on European Research

The European funding scheme from the FP7 offers the optimal framework for evaluating hypotension and its treatment in ELGAN. This study brings together a number of European partners whose primary aim is to make a positive impact on the health of our most vulnerable citizens and in doing so strengthen the role of Europe as a world leader in clinical research in this ever evolving field. A study that shows an effect of drugs on patients from diverse countries and different social backgrounds will gain a much greater external validity than one that is being performed in one country only with a resultant greater generalisation of the findings. We believe this study will have worldwide implications for the care of the ELGAN and would see Europe as leading the way.

Establishment of links with North American Researchers

Enhanced collaboration among European Neonatologists, Canadian Neonatologists and international Basic Scientists will evolve and create important synergies for future newborn studies. The paucity of adequate European trials in the neonatal population, and in particular the ELGAN, is due on the one hand to the enormous collaborative efforts required when studying such a unique population of patients and on the other hand due to the unique physiology and developmental diversity of the ELGAN infant. This process becomes even more difficult when long-term follow-up is included in the study protocol, a necessary requirement of any study. Canada has long been a leading centre for clinical research in the neonate. Some of the most recent multicentre trials in neonatal care have been coordinated in Canada neonatal centres. These include the TIPP trial, the CAP trial and the PINT trial and the current NIPPV trial. Our trial is a large multicentre RCT that brings together European researchers and Canadian researchers with expertise in neonatology, neonatal cardiology, neonatal neurophysiology, clinical trial methodology and conduct, as well as basic science. Future collaborative links will be established to answer other important questions in newborn care, particularly drug trials involving off-patent medications.