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
|Condition or disease|
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.
|Study Type :||Observational|
|Estimated Enrollment :||82 participants|
|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|
Adult COVID-19 patients admitted to intensive care units
- Change of plasma bio-adrenomedullin [ Time Frame: Day 1-7 after intensive care unit admission ]Change of plasma bio-adrenomedullin
- Change of plasma proenkephalin [ Time Frame: Day 1-7 after intensive care unit admission ]Change of plasma proenkephalin
- Change of plasma dipeptidyl peptidase-3 [ Time Frame: Day 1-7 after intensive care unit admission ]Change of plasma dipeptidyl peptidase-3
- Change of plasma renin [ Time Frame: Day 1-7 after intensive care unit admission ]Change of plasma renin
- Change of plasma angiotensin II [ Time Frame: Day 1-7 after intensive care unit admission ]Change of plasma angiotensin II
- Duration of vasodilatory shock [ Time Frame: 7 and 28 days ]Duration of vasodilatory shock
- Acute kidney injury [ Time Frame: 7 and 28 days ]As defined by the Kidney Disease: Improving Global Outcomes criteria
- Need for renal replacement therapy [ Time Frame: 7 and 28 days ]Need for renal replacement therapy
- Duration of ventilation [ Time Frame: 7 and 28 days ]Duration of ventilation
- Duration of extracorporeal membrane oxygenation [ Time Frame: 7 and 28 days ]Duration of extracorporeal membrane oxygenation
- Mortality [ Time Frame: 28 days ]ICU and hospital
Biospecimen Retention: Samples Without DNA
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
|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|
|Guy's & St Thomas' Hospital||Recruiting|
|London, United Kingdom, SE1 7EH|
|Contact: Marlies Ostermann, MD, PhD 020 71883038 Marlies.Ostermann@gstt.nhs.uk|
|Principal Investigator:||Nuttha Lumlertgul, MD, PhD||Guy's & St Thomas' Hospital|