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Markers of Inflammation and Lung Recovery in ECMO Patients for PPHN (Mi-ECMO)

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ClinicalTrials.gov Identifier: NCT02940327
Recruitment Status : Completed
First Posted : October 20, 2016
Results First Posted : March 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
Collaborators:
University Hospitals, Leicester
Heart Link Children's Charity
British Heart Foundation
Information provided by (Responsible Party):
University of Leicester

Study Description
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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.

Condition or disease
Persistent Pulmonary Hypertension of the Newborn

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
Study Design
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Layout table for study information
Study Type : Observational
Actual Enrollment : 24 participants
Observational Model: Case-Control
Time Perspective: Prospective
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 Start Date : February 19, 2016
Actual Primary Completion Date : July 10, 2017
Actual Study Completion Date : July 10, 2017

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. CD16/41 [ Time Frame: 12 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  2. CD16/41 [ Time Frame: 24 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  3. CD16/41 [ Time Frame: 48 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  4. CD16/41 [ Time Frame: 72 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  5. CD16/41 [ Time Frame: 24 hours after decannulation ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  6. CD14/41 [ Time Frame: 12 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  7. CD14/41 [ Time Frame: 24 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  8. CD14/41 [ Time Frame: 48 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  9. CD14/41 [ Time Frame: 72 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  10. CD14/41 [ Time Frame: 24 hours after ECMO decannulation ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  11. CD64/163 [ Time Frame: 12 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  12. CD64/163 [ Time Frame: 24 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  13. CD64/163 [ Time Frame: 48 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  14. CD64/163 [ Time Frame: 72 hours after ECMO commencement ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

  15. CD64/163 [ Time Frame: 24 hours after decannulation ]
    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.


Secondary Outcome Measures :
  1. Change of Serum Haemoglobin Levels [ Time Frame: baseline ]
    Clinical and biochemical markers of organ failure

  2. Duration on ECMO [ Time Frame: > 7 days or did not survive to discharge ]
    Clinical and biochemical markers of organ failure

  3. Number of Participants With Acute Kidney Injury [ Time Frame: >7 days or did not survive to discharge ]
    Clinical and biochemical markers of organ failure

  4. Heart Injury as Determined by Serum Troponin Levels [ Time Frame: 12 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  5. Allogenic Red Cell Transfusion Volume [ Time Frame: 24 hours after ECMO is discontinued ]
    Clinical and biochemical markers of organ failure

  6. Number of Participants Requiring Non Red Cell Transfusion [ Time Frame: 24 hours after ECMO is discontinued ]
    Clinical and biochemical markers of organ failure

  7. Heart Injury as Determined by Serum Troponin Levels [ Time Frame: 24 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  8. Heart Injury as Determined by Serum Troponin Levels [ Time Frame: 48 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  9. Heart Injury as Determined by Serum Troponin Levels [ Time Frame: 72 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  10. Heart Injury as Determined by Serum Troponin Levels [ Time Frame: 24 hours after decannulation ]
    Clinical and biochemical markers of organ failure

  11. Change of Serum Haemoglobin Levels [ Time Frame: 12 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  12. Change of Serum Haemoglobin Levels [ Time Frame: 24 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  13. Change of Serum Haemoglobin Levels [ Time Frame: 48 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  14. Change of Serum Haemoglobin Levels [ Time Frame: 72 hours after ECMO commencement ]
    Clinical and biochemical markers of organ failure

  15. Change of Serum Haemoglobin Levels [ Time Frame: 24 hours after decannulation ]
    Clinical and biochemical markers of organ failure


Biospecimen Retention:   Samples With DNA
Blood samples, Urine samples, Respiratory samples

Eligibility Criteria
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Layout table for eligibility information
Ages Eligible for Study:   up to 30 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02940327


Locations
Layout table for location information
United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, United Kingdom, LE3 9QP
Sponsors and Collaborators
University of Leicester
University Hospitals, Leicester
Heart Link Children's Charity
British Heart Foundation
  Study Documents (Full-Text)

Documents provided by University of Leicester:
Study Protocol  [PDF] February 27, 2017
Statistical Analysis Plan  [PDF] May 1, 2018

More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT02940327    
Other Study ID Numbers: 0553
First Posted: October 20, 2016    Key Record Dates
Results First Posted: March 19, 2020
Last Update Posted: March 19, 2020
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: statistical analysis
Keywords provided by University of Leicester:
ECMO
PPHN
Pulmonary Hypertension of the Newborn
Markers of inflammation
Mi-Ecmo
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Hypertension
Inflammation
Vascular Diseases
 Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases