Clinical trial NCT02940327: Markers of Inflammation and Lung Recovery in ECMO Patients for PPHN
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Persistent Pulmonary Hypertension of the Newborn
Keywords: ECMO
PPHN
Pulmonary Hypertension of the Newborn
Markers of inflammation
Mi-Ecmo
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: University Hospitals, Leicester
name: Heart Link Children's Charity
name: British Heart Foundation
First posted: 2016-10-20
Enrollment: 24
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be conducted at a regional ECMO centre in the UK, the University Hospitals of Leicester NHS Trust. This unit performs over 60 neonatal and paediatric ECMO per year, of which at least 40 are expected to be performed for the treatment of PPHN in infants.

Brief summary: 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: 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:

1. Damage to red cells will result in platelet, leukocyte and endothelial activation.
2. Markers of platelet, endothelial and leukocyte activation are indicators of lung inflammation and injury severity and hence lung recovery.
3. Markers of platelet, endothelial and leukocyte activation are indicators of kidney injury severity and hence acute kidney injury.
4. The level of oxidative stress will correlate with type shifts in pulmonary macrophages, tissue iron deposition and organ injury.
5. 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.
6. 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.
7. 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:

1. Recruitment rates and patient flows for 24 patients specified as the target population for the feasibility study
2. Withdrawal rate, and completeness of follow-up and data collection in a paediatric population at high risk for death and major morbidity
3. 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
4. Perceptions of family members whose children participate in the study as to the appropriateness of the screening and consent process

Eligibility criteria: Inclusion Criteria:

1. Patients with a diagnosis of PPHN
2. Patients that require ECMO support as determined by the ECMO team
3. Patients aged less than 30 days
4. Emergency consent obtained within 12 hours from cannulation, and ultimately full consent

Exclusion Criteria:

1. PPHN is caused by a congenital heart pathology
2. ECMO is required for a congenital heart disease
3. Lack of consent

Primary outcomes:
measure: CD16/41
timeFrame: 12 hours after ECMO commencement
measure: CD16/41
timeFrame: 24 hours after ECMO commencement
measure: CD16/41
timeFrame: 48 hours after ECMO commencement
measure: CD16/41
timeFrame: 72 hours after ECMO commencement
measure: CD16/41
timeFrame: 24 hours after decannulation
measure: CD14/41
timeFrame: 12 hours after ECMO commencement
measure: CD14/41
timeFrame: 24 hours after ECMO commencement
measure: CD14/41
timeFrame: 48 hours after ECMO commencement
measure: CD14/41
timeFrame: 72 hours after ECMO commencement
measure: CD14/41
timeFrame: 24 hours after ECMO decannulation
measure: CD64/163
timeFrame: 12 hours after ECMO commencement
measure: CD64/163
timeFrame: 24 hours after ECMO commencement
measure: CD64/163
timeFrame: 48 hours after ECMO commencement
measure: CD64/163
timeFrame: 72 hours after ECMO commencement
measure: CD64/163
timeFrame: 24 hours after decannulation
Secondary outcomes:
measure: Change of Serum Haemoglobin Levels
timeFrame: baseline
measure: Duration on ECMO
timeFrame: > 7 days or did not survive to discharge
measure: Number of Participants With Acute Kidney Injury
timeFrame: >7 days or did not survive to discharge
measure: Heart Injury as Determined by Serum Troponin Levels
timeFrame: 12 hours after ECMO commencement
measure: Allogenic Red Cell Transfusion Volume
timeFrame: 24 hours after ECMO is discontinued
measure: Number of Participants Requiring Non Red Cell Transfusion
timeFrame: 24 hours after ECMO is discontinued
measure: Heart Injury as Determined by Serum Troponin Levels
timeFrame: 24 hours after ECMO commencement
measure: Heart Injury as Determined by Serum Troponin Levels
timeFrame: 48 hours after ECMO commencement
measure: Heart Injury as Determined by Serum Troponin Levels
timeFrame: 72 hours after ECMO commencement
measure: Heart Injury as Determined by Serum Troponin Levels
timeFrame: 24 hours after decannulation
measure: Change of Serum Haemoglobin Levels
timeFrame: 12 hours after ECMO commencement
measure: Change of Serum Haemoglobin Levels
timeFrame: 24 hours after ECMO commencement
measure: Change of Serum Haemoglobin Levels
timeFrame: 48 hours after ECMO commencement
measure: Change of Serum Haemoglobin Levels
timeFrame: 72 hours after ECMO commencement
measure: Change of Serum Haemoglobin Levels
timeFrame: 24 hours after decannulation
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
Study officials:
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