NeoAdapt 3: An Observational Study Investigating Novel Biomarkers in the Evaluation and Treatment of Neonatal Circulatory Insufficiency in Infants Suffering From Hypoxic Ischemic Encephalopathy.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Superior Vena Cava Flow (SVCF) in babys recieving total body cooling for Hypoxic Ischemic Encephalopathy
Study Overview
Brief Summary
1 in 1000 babies are born suffering from a lack of oxygen. This is known as hypoxic ischemic encephalopathy (HIE). Infants with this condition can suffer multiple organ problems. In particular it can affect how their hearts pump blood around their body thus leading to a poor blood supply to parts of their body such as the brain. This is known as circulatory failure and can contribute to poor long term outcomes such as cerebral palsy. To try and prevent brain damage these infants are treated with total body cooling, however this treatment can further effect how babies pump blood around the body, but also how drugs which may be used by in this condition are processed.
In order to assess and treat this condition doctors need to be able to accurately measure the blood supply in an infant. However there is no agreement on how best to do this. This makes decisions about when to treat an infant difficult. Sometimes doctors may want to use drugs such as dobutamine or adrenaline but these drugs are unlicensed in babies.
This study proposes to observe the way babies circulatory problems are treated in babies with HIE the in the first four days of life. In addition the study will look are two new measurements of a babies blood supply to see if they are a better measure of when an infant needs treatment. This will involve an ultrasound scan of the heart and measurement of the baby's oxygen levels from a probe placed on their hand. The study will also look at how the drug dobutamine is processed by babies. This will be done from two small extra blood tests. The aim of the study is to help clinicians refine the identification and treatment of circulatory failure in babies with HIE.
Detailed Description
The current definitions of neonatal shock/circulatory failure are outdated, inaccurate and it is not be appropriate to apply to infants suffering from hypoxic ischemic encephalopathy he purpose of the this research is to look at older than 33 weeks gestational age in order to fill the knowledge gap here and help in the development a new definition of neonatal circulatory failure.
The main research questions are:-
- To investigate new non-invasive methods of assessing an infants circulatory status in infants suffering from HIE.
- To gain initial data on how dobutamine is processed by babies when they are used for circulatory failure.
- To observe how physicians decide to treat circulatory failure in infants suffering from HIE.
Research has shown that there is up to a 14 fold difference in how doctors assess and treat circulatory failure. In infants suffering from hypoxic ischemic encephalopathy this is complicated further by the fact that treatment with total body cooling can interfere further with how the body pumps blood around the body. This is further complicated by the fact there is no agreed definition for circulatory failure in infants. By investigating new methods of assessing a babies circulatory status we intend to help create a new definition of circulatory failure which will in turn help doctors create further studies to identify infants with circulatory failure and find the best ways of treating this condition in babies. So far research in this area has been concentrated in babies born at less than 33 weeks gestation. We extend the knowledge in the area to infants older that 36 weeks gestation suffering from hypoxic ischemic encephalopathy.
Dobutamine is a drug that does not have a license for use in infants. In the future all new drugs will need to be studied in children before a license for them is given. In addition the European Community are encouraging that research is undertaken to look into the use of old drugs in which are used in babies. As mentioned previously there is very little data to show how dobutamine is handled by babies and contribute to new information on how this drug should be given safely.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- — to 3 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Infants admitted to the NICU with HIE for total body cooling therapy
- •Postnatal age <72 hours
- •Parental informed consent
Exclusion Criteria
- •Non-viability
- •Congenital hydrops or malformations likely to affect cardiovascular adaptation
- •Surgery planned within 72 hours of birth
- •Chromosomal anomalies
- •Informed consent form (ICF) not signed
Arms & Interventions
HIE Group
Intervention: Dobutamine (Drug)
Outcomes
Primary Outcomes
Superior Vena Cava Flow (SVCF) in babys recieving total body cooling for Hypoxic Ischemic Encephalopathy
Time Frame: Once a day for a maximum of three days after birth
After consent and enrolment, Echo-D assessments will be repeated every 24 of cooling treatment (first 72 hours of postnatal life) and once during the re-warming phase (typically taking 8 hours after cooling has finished). The change in this measurement over the cooling treatment will be recorded.
Pleth Variability Index (PVI) in infants undergoing total body cooling treatment for hypoxic ischemic encephalopathy
Time Frame: Once a day for a maximum of three days after birth
After consent and enrolment PVI assessments will be repeated every 24 of cooling treatment (first 72 hours of postnatal life) and once during the re-warming phase (typically taking 8 hours after cooling has finished). The changes in the PVI measurements will be recorded over the course of cooling therapy.
Pharmacokinetic data for the emilmination half life of dobutamine when this drug is given for circulatory failure
Time Frame: If dobutamine is given to an infant in the first three days of life
If dobutamine is given for circulatory insufficiency in the first three days of life 2 blood samples will be taken for pharmacokinetic analysis of dobutamine.
Secondary Outcomes
- SVCF and PVI values corrleation to each other and to parameters that assess circulatory status such as mean blood pressure and capillary refill time(Over the first 3 days of life)
- SVCF and PVI values and dobutamine treatment for circulatory failure(Over the first three days of life)
- SVCF and PVI values relationship to clinical outcomes(Over the first three days of life)
Investigators
Dr Liam Mahoney
Clinical Research Fellow in Paediatrics
Brighton and Sussex University Hospitals NHS Trust