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Endothelial Function, Inflammation and Organ Dysfunction in COVID-19

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ClinicalTrials.gov Identifier: NCT04408365
Recruitment Status : Recruiting
First Posted : May 29, 2020
Last Update Posted : August 9, 2021
Sponsor:
Collaborator:
King's College Hospital NHS Trust
Information provided by (Responsible Party):
Guy's and St Thomas' NHS Foundation Trust

Brief Summary:
COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients which require intensive care unit admission. In critically ill patients infected with COVID-19, approximately 15% had severe shock requiring medications to increase blood pressure. It appears that blood vessel tone is altered and microcirculation is not well regulated in patients with COVID-19. The underlying pathophysiology and contributing factors are unknown. The association with subsequent organ dysfunction and outcome is also unclear. Therefore, the investigators aim to investigate serial changes of relevant biomarkers in this population to improve the understanding of this disease, to investigate the association with clinically important outcomes and to find out how best to treat patients. The data will serve to develop strategies for individualised management of this high-risk group.

Condition or disease
COVID Shock

Detailed Description:

COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients requiring admission to an intensive care unit. In critically ill patients infected with COVID-19, acute respiratory distress syndrome (ARDS) is found in 40%, 11.9% required continuous renal replacement therapy (RRT), and 13.4% had vasodilatory shock.

Currently, supportive treatment is the mainstay treatment, with fluid administration and vasopressors for haemodynamic support and lung-protective ventilation in patients with severe respiratory failure.3 Targeted drugs, antiviral therapies, and vaccines are still currently being developed, but there is currently insufficient evidence to recommend any drug over another.

Dysregulation of vasomotor tone and alteration of microcirculatory function are common in patients infected with COVID-19. The underlying pathophysiology and contributing factors are unknown. The association with subsequent organ dysfunction and outcome is also unclear.

Circulating bio-adrenomedullin regulates vascular tone and endothelial permeability during sepsis, and has been shown to associate with 28-day mortality, vasopressor requirement, RRT, and positive fluid balance. Proenkephalin is a biomarker of glomerular function, and was shown to elevate in patients with acute kidney injury (AKI), especially in those with persistent AKI, and major adverse kidney events. Dipeptidyl peptidase 3 (DPP-3) is a myocardial depressant factor, which is involved in angiotensin II cleavage. High DPP-3 levels were associated with severe organ dysfunction and short-term mortality. In critically ill patients, COVID-19 has been reported to be associated with cardiovascular dysfunction and high mortality.

The renin-angiotensin-aldosterone system (RAAS) may be linked to the pathogenesis of COVID-19. The coronavirus receptor utilizes angiotensin converting enzyme 2 (ACE2) to enter target cells. Endogenous angiotensin II is hypothesized to prevent binding of coronavirus to ACE2, causing internalization and downregulation of ACE2, and causing lysosome-mediated destruction of ACE2. There are no human studies in COVID-19 patients to confirm this hypothesis yet.

There is very little knowledge of underlying pathogenesis in patients with COVID-19 and vasodilatory shock. Therefore, the investigators aim to investigate serial changes of relevant biomarkers in this population to give further understanding of this disease and to investigate the association with clinically important outcomes. The data will serve to develop strategies for individualized management of this high-risk group.

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Study Type : Observational
Estimated Enrollment : 82 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Endothelial Function, Inflammation, and Organ Dysfunction in Critically Ill Patients With COVID-19
Actual Study Start Date : August 5, 2020
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Group/Cohort
COVID-19 patients
Adult COVID-19 patients admitted to intensive care units



Primary Outcome Measures :
  1. Change of plasma bio-adrenomedullin [ Time Frame: Day 1-7 after intensive care unit admission ]
    Change of plasma bio-adrenomedullin

  2. Change of plasma proenkephalin [ Time Frame: Day 1-7 after intensive care unit admission ]
    Change of plasma proenkephalin

  3. Change of plasma dipeptidyl peptidase-3 [ Time Frame: Day 1-7 after intensive care unit admission ]
    Change of plasma dipeptidyl peptidase-3

  4. Change of plasma renin [ Time Frame: Day 1-7 after intensive care unit admission ]
    Change of plasma renin

  5. Change of plasma angiotensin II [ Time Frame: Day 1-7 after intensive care unit admission ]
    Change of plasma angiotensin II


Secondary Outcome Measures :
  1. Duration of vasodilatory shock [ Time Frame: 7 and 28 days ]
    Duration of vasodilatory shock

  2. Acute kidney injury [ Time Frame: 7 and 28 days ]
    As defined by the Kidney Disease: Improving Global Outcomes criteria

  3. Need for renal replacement therapy [ Time Frame: 7 and 28 days ]
    Need for renal replacement therapy

  4. Duration of ventilation [ Time Frame: 7 and 28 days ]
    Duration of ventilation

  5. Duration of extracorporeal membrane oxygenation [ Time Frame: 7 and 28 days ]
    Duration of extracorporeal membrane oxygenation

  6. Mortality [ Time Frame: 28 days ]
    ICU and hospital


Biospecimen Retention:   Samples Without DNA
Daily blood samples from ICU admission until day 7 and around the onset of vasodilatory shock Daily urine and RRT effluent fluid samples (if available) from ICU admission until day 7


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adult COVID-19 patients who are admitted in intensive care units
Criteria

Inclusion Criteria:

  1. Adult patients (≥ 18 years old) admitted to intensive care units
  2. Confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection resulting in coronavirus disease 2019 (COVID-19)

Exclusion Criteria:

None


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): NCT04408365


Contacts
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Contact: Marlies Ostermann, MD, PhD 0044 207 188 3038 ext 83036 Marlies.Ostermann@gstt.nhs.uk
Contact: Nuttha Lumlertgul, MD, PhD 0044 207 188 3038 ext 83036 Nuttha.Lumlertgul@gstt.nhs.uk

Locations
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United Kingdom
Guy's & St Thomas' Hospital Recruiting
London, United Kingdom, SE1 7EH
Contact: Marlies Ostermann, MD, PhD    020 71883038    Marlies.Ostermann@gstt.nhs.uk   
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
King's College Hospital NHS Trust
Investigators
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Principal Investigator: Nuttha Lumlertgul, MD, PhD Guy's & St Thomas' Hospital
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Responsible Party: Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04408365    
Other Study ID Numbers: 282930
First Posted: May 29, 2020    Key Record Dates
Last Update Posted: August 9, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes