Markers of Inflammation and Lung Recovery in ECMO Patients for PPHN

Study Overview
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Brief Summary
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Respiratory failure in newborns is common and has high rates of death. Where conventional intensive care strategies have failed, newborn children are referred to treatment with Extra- Corporeal Membrane Oxygenation (ECMO). This involves connecting children via large bore cannulas placed in their heart and major blood vessels to an artificial lung that adds oxygen to their blood and removes waste gases (carbon dioxide). Although this treatment saves lives, it still has some limitations. In particular, severe complications like bleeding, or damage to the kidneys can occur. These complications can lead to death in some cases and long-term disability in others. Based on ongoing research in adults and children undergoing cardiac surgery the investigators have identified a new process that may underlie some of the complications observed in ECMO. The investigators have noted that when transfused blood is infused in an ECMO circuit, this results in the accelerated release of substances from the donor cells that cause organ damage; at least in adults. There are treatments that can reverse this process. Before the investigators explore whether these treatments should be used in newborn children on ECMO, the investigators must first demonstrate that they can measure the complex inflammatory processes that occur in these critically ill children. The investigators therefore propose to conduct a feasibility study to identify the practical issues and challenges that would need to be overcome in order to perform a successful trial in this high-risk population.

Detailed Description
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The primary hypothesis is that damage to red blood cells by the exposure to the ECMO circuit will result in inflammatory responses that mitigate against successful weaning from Extra-Corporeal Membrane Oxygenation (ECMO) for Persistent Pulmonary Hypertension of the Newborn (PPHN). The secondary hypothesis are: Damage to red cells will result in platelet, leukocyte and endothelial activation. Markers of platelet, endothelial and leukocyte activation are indicators of lung inflammation and injury severity and hence lung recovery. Markers of platelet, endothelial and leukocyte activation are indicators of kidney injury severity and hence acute kidney injury. The level of oxidative stress will correlate with type shifts in pulmonary macrophages, tissue iron deposition and organ injury. Ability to raise anti-oxidative response, measured by Heme Oxigenase-1 (HMOX 1) expression, will correlate with shorter intubation times and less severe kidney and lung injury. Granulocyte and platelets activation are secondary to rising redox potential and the levels of activation will correlate with longer intubation times and more severe organ injury. Markers of anti-oxidative response, platelet, endothelial and leukocyte activation, as well as oxidative stress levels have diagnostic and prognostic utility for the prediction of key clinical events including delayed time to recovery, acute kidney injury in paediatric patients undergoing Extra-Corporeal Membrane Oxygenation (ECMO) for Persistent Pulmonary Hypertension of the Newborn (PPHN). This is a pilot feasibility study that will establish the following: Recruitment rates and patient flows for 24 patients specified as the target population for the feasibility study Withdrawal rate, and completeness of follow-up and data collection in a paediatric population at high risk for death and major morbidity The proportions (categorical data) and variance (continuous data) for the primary and secondary outcomes of interest. These will be used to model the sample sizes and outcomes that may be used in a definitive study Perceptions of family members whose children participate in the study as to the appropriateness of the screening and consent process

Official Title
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A Feasibility Study to Consider the Relationship Between Markers of Red Cell Damage, Inflammation and the Recovery Process of Newborns Requiring Extracorporeal Membrane Oxygenation (ECMO) for Persistent Pulmonary Hypertension of the Newborn (PPHN): Mi-ECMO

Conditions
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Persistent Pulmonary Hypertension of the Newborn

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of PPHN Patients that require ECMO support as determined by the ECMO team Patients aged less than 30 days Emergency consent obtained within 12 hours from cannulation, and ultimately full consent Exclusion Criteria: PPHN is caused by a congenital heart pathology ECMO is required for a congenital heart disease Lack of consent

Ages Eligible for Study
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Maximum Age: 30 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD16/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 12 hours after ECMO commencement | 
| CD16/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 24 hours after ECMO commencement | 
| CD16/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 48 hours after ECMO commencement | 
| CD16/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 72 hours after ECMO commencement | 
| CD16/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 24 hours after decannulation | 
| CD14/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 12 hours after ECMO commencement | 
| CD14/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 24 hours after ECMO commencement | 
| CD14/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 48 hours after ECMO commencement | 
| CD14/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 72 hours after ECMO commencement | 
| CD14/41 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 24 hours after ECMO decannulation | 
| CD64/163 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 12 hours after ECMO commencement | 
| CD64/163 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 24 hours after ECMO commencement | 
| CD64/163 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 48 hours after ECMO commencement | 
| CD64/163 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 72 hours after ECMO commencement | 
| CD64/163 | Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry. | 24 hours after decannulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Serum Haemoglobin Levels | Clinical and biochemical markers of organ failure | baseline | 
| Duration on ECMO | Clinical and biochemical markers of organ failure | > 7 days or did not survive to discharge | 
| Number of Participants With Acute Kidney Injury | Clinical and biochemical markers of organ failure | >7 days or did not survive to discharge | 
| Heart Injury as Determined by Serum Troponin Levels | Clinical and biochemical markers of organ failure | 12 hours after ECMO commencement | 
| Allogenic Red Cell Transfusion Volume | Clinical and biochemical markers of organ failure | 24 hours after ECMO is discontinued | 
| Number of Participants Requiring Non Red Cell Transfusion | Clinical and biochemical markers of organ failure | 24 hours after ECMO is discontinued | 
| Heart Injury as Determined by Serum Troponin Levels | Clinical and biochemical markers of organ failure | 24 hours after ECMO commencement | 
| Heart Injury as Determined by Serum Troponin Levels | Clinical and biochemical markers of organ failure | 48 hours after ECMO commencement | 
| Heart Injury as Determined by Serum Troponin Levels | Clinical and biochemical markers of organ failure | 72 hours after ECMO commencement | 
| Heart Injury as Determined by Serum Troponin Levels | Clinical and biochemical markers of organ failure | 24 hours after decannulation | 
| Change of Serum Haemoglobin Levels | Clinical and biochemical markers of organ failure | 12 hours after ECMO commencement | 
| Change of Serum Haemoglobin Levels | Clinical and biochemical markers of organ failure | 24 hours after ECMO commencement | 
| Change of Serum Haemoglobin Levels | Clinical and biochemical markers of organ failure | 48 hours after ECMO commencement | 
| Change of Serum Haemoglobin Levels | Clinical and biochemical markers of organ failure | 72 hours after ECMO commencement | 
| Change of Serum Haemoglobin Levels | Clinical and biochemical markers of organ failure | 24 hours after decannulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, PPHN, Pulmonary Hypertension of the Newborn, Markers of inflammation, Mi-Ecmo