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

March 4, 2020 updated by: University of Leicester

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

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.

Study Overview

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 Type

Observational

Enrollment (Actual)

24

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Leicester, United Kingdom, LE3 9QP
        • University Hospitals Of Leicester Nhs Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 weeks (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 hours after ECMO commencement
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.
24 hours after ECMO commencement
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.
48 hours after ECMO commencement
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.
72 hours after ECMO commencement
CD16/41
Time Frame: 24 hours after decannulation
Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.
24 hours after decannulation
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.
12 hours after ECMO commencement
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.
24 hours after ECMO commencement
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.
48 hours after ECMO commencement
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.
72 hours after ECMO commencement
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.
24 hours after ECMO decannulation
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 hours after ECMO commencement
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.
24 hours after ECMO commencement
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.
48 hours after ECMO commencement
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.
72 hours after ECMO commencement
CD64/163
Time Frame: 24 hours after decannulation
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
Time Frame: baseline
Clinical and biochemical markers of organ failure
baseline
Duration on ECMO
Time Frame: > 7 days or did not survive to discharge
Clinical and biochemical markers of organ failure
> 7 days or did not survive to discharge
Number of Participants With Acute Kidney Injury
Time Frame: >7 days or did not survive to discharge
Clinical and biochemical markers of organ failure
>7 days or did not survive to discharge
Heart Injury as Determined by Serum Troponin Levels
Time Frame: 12 hours after ECMO commencement
Clinical and biochemical markers of organ failure
12 hours after ECMO commencement
Allogenic Red Cell Transfusion Volume
Time Frame: 24 hours after ECMO is discontinued
Clinical and biochemical markers of organ failure
24 hours after ECMO is discontinued
Number of Participants Requiring Non Red Cell Transfusion
Time Frame: 24 hours after ECMO is discontinued
Clinical and biochemical markers of organ failure
24 hours after ECMO is discontinued
Heart Injury as Determined by Serum Troponin Levels
Time Frame: 24 hours after ECMO commencement
Clinical and biochemical markers of organ failure
24 hours after ECMO commencement
Heart Injury as Determined by Serum Troponin Levels
Time Frame: 48 hours after ECMO commencement
Clinical and biochemical markers of organ failure
48 hours after ECMO commencement
Heart Injury as Determined by Serum Troponin Levels
Time Frame: 72 hours after ECMO commencement
Clinical and biochemical markers of organ failure
72 hours after ECMO commencement
Heart Injury as Determined by Serum Troponin Levels
Time Frame: 24 hours after decannulation
Clinical and biochemical markers of organ failure
24 hours after decannulation
Change of Serum Haemoglobin Levels
Time Frame: 12 hours after ECMO commencement
Clinical and biochemical markers of organ failure
12 hours after ECMO commencement
Change of Serum Haemoglobin Levels
Time Frame: 24 hours after ECMO commencement
Clinical and biochemical markers of organ failure
24 hours after ECMO commencement
Change of Serum Haemoglobin Levels
Time Frame: 48 hours after ECMO commencement
Clinical and biochemical markers of organ failure
48 hours after ECMO commencement
Change of Serum Haemoglobin Levels
Time Frame: 72 hours after ECMO commencement
Clinical and biochemical markers of organ failure
72 hours after ECMO commencement
Change of Serum Haemoglobin Levels
Time Frame: 24 hours after decannulation
Clinical and biochemical markers of organ failure
24 hours after decannulation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 19, 2016

Primary Completion (Actual)

July 10, 2017

Study Completion (Actual)

July 10, 2017

Study Registration Dates

First Submitted

October 13, 2016

First Submitted That Met QC Criteria

October 18, 2016

First Posted (Estimate)

October 20, 2016

Study Record Updates

Last Update Posted (Actual)

March 19, 2020

Last Update Submitted That Met QC Criteria

March 4, 2020

Last Verified

May 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

statistical analysis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Persistent Pulmonary Hypertension of the Newborn

3
Subscribe