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Persistent Pulmonary Hypertension of the NewbornMi-ECMONCT02940327

Markers of Inflammation and Lung Recovery in ECMO Patients for PPHN

An observational study of Persistent Pulmonary Hypertension of the Newborn, run by University of Leicester at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages Up to 30 days
How many people
24 participants
Where
1 siteUnited Kingdom
Study dates
19 Feb 2016to 10 Jul 2017
Phase
Observational
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 days
  • All sexes
  • No healthy volunteers
  • Child

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.

Who may be able to join

  • 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

Who cannot join

  • PPHN is caused by a congenital heart pathology
  • ECMO is required for a congenital heart disease
  • Lack of consent

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • University Hospitals of Leicester NHS Trust

    Leicester, LE3 9QP

Other trials in United Kingdom

About this study

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

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.

Read the 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
Keywords
ECMO, PPHN, Pulmonary Hypertension of the Newborn, Markers of inflammation, Mi-Ecmo
Medical subject headings
Persistent Fetal Circulation Syndrome

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CD16/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 12 hours after ECMO commencement

  2. CD16/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 24 hours after ECMO commencement

  3. CD16/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 48 hours after ECMO commencement

  4. CD16/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 72 hours after ECMO commencement

  5. CD16/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 24 hours after decannulation

  6. CD14/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 12 hours after ECMO commencement

  7. CD14/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 24 hours after ECMO commencement

  8. CD14/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 48 hours after ECMO commencement

  9. CD14/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 72 hours after ECMO commencement

  10. CD14/41

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 24 hours after ECMO decannulation

  11. CD64/163

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 12 hours after ECMO commencement

  12. CD64/163

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 24 hours after ECMO commencement

  13. CD64/163

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 48 hours after ECMO commencement

  14. CD64/163

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 72 hours after ECMO commencement

  15. CD64/163

    Change of markers of platelet and leukocyte activation in arterial blood and analysed by flow cytometry.

    Measured: 24 hours after decannulation

Secondary outcomes (15)
  1. Change of Serum Haemoglobin Levels

    Clinical and biochemical markers of organ failure

    Measured: baseline

  2. Duration on ECMO

    Clinical and biochemical markers of organ failure

    Measured: > 7 days or did not survive to discharge

  3. Number of Participants With Acute Kidney Injury

    Clinical and biochemical markers of organ failure

    Measured: >7 days or did not survive to discharge

  4. Heart Injury as Determined by Serum Troponin Levels

    Clinical and biochemical markers of organ failure

    Measured: 12 hours after ECMO commencement

  5. Allogenic Red Cell Transfusion Volume

    Clinical and biochemical markers of organ failure

    Measured: 24 hours after ECMO is discontinued

  6. Number of Participants Requiring Non Red Cell Transfusion

    Clinical and biochemical markers of organ failure

    Measured: 24 hours after ECMO is discontinued

  7. Heart Injury as Determined by Serum Troponin Levels

    Clinical and biochemical markers of organ failure

    Measured: 24 hours after ECMO commencement

  8. Heart Injury as Determined by Serum Troponin Levels

    Clinical and biochemical markers of organ failure

    Measured: 48 hours after ECMO commencement

  9. Heart Injury as Determined by Serum Troponin Levels

    Clinical and biochemical markers of organ failure

    Measured: 72 hours after ECMO commencement

  10. Heart Injury as Determined by Serum Troponin Levels

    Clinical and biochemical markers of organ failure

    Measured: 24 hours after decannulation

  11. Change of Serum Haemoglobin Levels

    Clinical and biochemical markers of organ failure

    Measured: 12 hours after ECMO commencement

  12. Change of Serum Haemoglobin Levels

    Clinical and biochemical markers of organ failure

    Measured: 24 hours after ECMO commencement

  13. Change of Serum Haemoglobin Levels

    Clinical and biochemical markers of organ failure

    Measured: 48 hours after ECMO commencement

  14. Change of Serum Haemoglobin Levels

    Clinical and biochemical markers of organ failure

    Measured: 72 hours after ECMO commencement

  15. Change of Serum Haemoglobin Levels

    Clinical and biochemical markers of organ failure

    Measured: 24 hours after decannulation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2016 (estimated)
  2. Study start19 Feb 2016
  3. Primary completion10 Jul 2017
  4. Study completion10 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02940327
Sponsor's protocol ID
0553
Acronym
Mi-ECMO
Status last verified
May 2018
First submitted
13 Oct 2016
Last updated
19 Mar 2020
Data monitoring committee
No
Individual data sharing
Yes: statistical analysis

Publications

  • Mamikonian LS, Mamo LB, Smith PB, Koo J, Lodge AJ, Turi JL. Cardiopulmonary bypass is associated with hemolysis and acute kidney injury in neonates, infants, and children*. Pediatr Crit Care Med. 2014 Mar;15(3):e111-9. doi: 10.1097/PCC.0000000000000047.

    PubMed 24394997
  • Schaible T, Hermle D, Loersch F, Demirakca S, Reinshagen K, Varnholt V. A 20-year experience on neonatal extracorporeal membrane oxygenation in a referral center. Intensive Care Med. 2010 Jul;36(7):1229-34. doi: 10.1007/s00134-010-1886-5. Epub 2010 Apr 28.

    PubMed 20425105
  • Mugford M, Elbourne D, Field D. Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants. Cochrane Database Syst Rev. 2008 Jul 16;2008(3):CD001340. doi: 10.1002/14651858.CD001340.pub2.

    PubMed 18646070
  • Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am. 2009 Jun;56(3):579-600, Table of Contents. doi: 10.1016/j.pcl.2009.04.004.

    PubMed 19501693
  • Bahrami KR, Van Meurs KP. ECMO for neonatal respiratory failure. Semin Perinatol. 2005 Feb;29(1):15-23. doi: 10.1053/j.semperi.2005.02.004.

    PubMed 15921148
  • UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. UK Collaborative ECMO Trail Group. Lancet. 1996 Jul 13;348(9020):75-82.

    PubMed 8676720
  • Zwiers AJ, de Wildt SN, Hop WC, Dorresteijn EM, Gischler SJ, Tibboel D, Cransberg K. Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study. Crit Care. 2013 Jul 24;17(4):R151. doi: 10.1186/cc12830.

    PubMed 23883698
  • Lazar DA, Cass DL, Olutoye OO, Welty SE, Fernandes CJ, Rycus PT, Lee TC. The use of ECMO for persistent pulmonary hypertension of the newborn: a decade of experience. J Surg Res. 2012 Oct;177(2):263-7. doi: 10.1016/j.jss.2012.07.058. Epub 2012 Aug 10.

    PubMed 22901797
  • McNally H, Bennett CC, Elbourne D, Field DJ; UK Collaborative ECMO Trial Group. United Kingdom collaborative randomized trial of neonatal extracorporeal membrane oxygenation: follow-up to age 7 years. Pediatrics. 2006 May;117(5):e845-54. doi: 10.1542/peds.2005-1167. Epub 2006 Apr 24.

    PubMed 16636114
  • Farrow KN, Fliman P, Steinhorn RH. The diseases treated with ECMO: focus on PPHN. Semin Perinatol. 2005 Feb;29(1):8-14. doi: 10.1053/j.semperi.2005.02.003.

    PubMed 15921147
  • Bendapudi P, Rao GG, Greenough A. Diagnosis and management of persistent pulmonary hypertension of the newborn. Paediatr Respir Rev. 2015 Jun;16(3):157-61. doi: 10.1016/j.prrv.2015.02.001. Epub 2015 Feb 10.

    PubMed 25765845
  • Puthiyachirakkal M, Mhanna MJ. Pathophysiology, management, and outcome of persistent pulmonary hypertension of the newborn: a clinical review. Front Pediatr. 2013 Sep 2;1:23. doi: 10.3389/fped.2013.00023.

    PubMed 24400269
  • McILwain RB, Timpa JG, Kurundkar AR, Holt DW, Kelly DR, Hartman YE, Neel ML, Karnatak RK, Schelonka RL, Anantharamaiah GM, Killingsworth CR, Maheshwari A. Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine. Lab Invest. 2010 Jan;90(1):128-39. doi: 10.1038/labinvest.2009.119. Epub 2009 Nov 9.

    PubMed 19901912
  • Fortenberry JD, Bhardwaj V, Niemer P, Cornish JD, Wright JA, Bland L. Neutrophil and cytokine activation with neonatal extracorporeal membrane oxygenation. J Pediatr. 1996 May;128(5 Pt 1):670-8. doi: 10.1016/s0022-3476(96)80133-8.

    PubMed 8627440
  • Mildner RJ, Taub N, Vyas JR, Killer HM, Firmin RK, Field DJ, Kotecha S. Cytokine imbalance in infants receiving extracorporeal membrane oxygenation for respiratory failure. Biol Neonate. 2005;88(4):321-7. doi: 10.1159/000087630. Epub 2005 Aug 18.

    PubMed 16113527

Questions about this trial

What is this clinical trial studying?

An observational study of Persistent Pulmonary Hypertension of the Newborn, run by University of Leicester at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CD16/41 (time frame: 12 hours after ECMO commencement). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02940327, which also lists 58 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2020.

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