COVIDNCT04399603
Mechanisms of Multi-organ Failure in COVID-19
An observational study of COVID, run by Imperial College London at 2 sites in United Kingdom.
Trial summary
In the United Kingdom, there are currently 138,000 confirmed patients with coronavirus, causing 18,738 deaths. Whilst the disease may be mild in the majority of patients, a significant proportion of patients require intensive care therapy and a ventilator due to lung injury. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- COVID
- How many people
- 120 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Jun 2020to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Critically unwell patients requiring organ support
Who may be able to join
- Male and female patients aged 18-90 years;
- Patients diagnosed with COVID-19 and without COVID-19 (control purposes);
- Patients who have developed evidence of organ injury failure (requiring oxygen).
Who cannot join
- Patients who are under the age of 18;
- Refusal to consent/gain assent;
- Presence of an advanced directive to withhold or to withdraw life-sustaining treatment;
- Moribund patient likely to die within 24 hours.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
Chelsea and Westminster Hospital NHS Foundation Trust
London
Roger Davies, 020 3315 8000, roger.davies@imperial.ac.uk
Roger Davies
- Recruiting
Imperial College NHS Trust
London
Sanooj Soni, PhD, 020 3313 1000, s.soni@imperial.ac.uk
Masao Takata
About this study
Official title: Multi-organ Failure in SARS-CoV2: Identifying Mechanisms and Potential Therapeutic Targets
In the United Kingdom, there are currently 138,000 confirmed patients with coronavirus, causing 18,738 deaths. Whilst the disease may be mild in the majority of patients, a significant proportion of patients require intensive care therapy and a ventilator due to lung injury. In addition to lung injury/failure (acute respiratory distress syndrome (ARDS)), around 50% of patients admitted to intensive care develop acute kidney injury (AKI) (requiring advanced support via haemofiltration) and multi-organ failure.
It is unclear why patients suffering from COVID-19 develop such severe lung injury (requiring life support or ventilation) or indeed why patients develop other organ dysfunction such as kidney injury. The investigators hypothesis that this may due to an over-reaction of the immune system particularly in the lungs. This then results in the release of various mediators and biological messengers which can be pushed into the blood bloodstream (exacerbated by positive pressure generated by the ventilator). These mediators then travel, via the blood, to other organs such as the kidney where they cause inflammation and injury of cells, resulting in organ failure.
The investigators would like to apply their well-established laboratory methods to further the scientific community's knowledge of this severe and deadly viral condition and we hope that this would lead to the development of medication that would treat this deadly virus.
Read the detailed description
COVID-19 is a highly contagious virus, causing a global health emergency. A significant number (~17%) of hospitalised patients become severely unwell and require admission to an intensive care unit (ICU) due to lung failure (acute respiratory distress syndrome (ARDS)) and multi-organ failure (MOF). Sadly, 51.8% of COVID-ARDS patients develop kidney failure, which has a markedly increased risk of dying (61%). We have learned that kidney failure starts several days after lung failure, which suggest an initial viral "attack" on the lungs followed by kidney involvement several days later.
Cytokines are "signalling" molecules made by cells, which in healthy individuals help fight disease. It was initially thought that in COVID-19, lung cells release excessive cytokines (i.e. cytokine storm), which then cause kidney injury and MOF. However, research has demonstrated that cytokine levels in blood are actually very low and not enough to explain the extent of organ injury in COVID-19. This perhaps explains why treatment strategies aimed at specifically damping down the action of these particular cytokines in COVID-19 have failed. Consequently, there remains no cure for COVID-19 MOF, and whilst treatments such as steroids, manage symptoms, have a general anti-inflammatory effect and improve mortality, 30% of intensive care patients still die. Therefore, urgent research is needed to improve scientific knowledge of this condition and identify new therapies.
Microvesicles (MVs) are extremely small particles released by cells and carry various chemicals including cytokines, from inside the cell, packaged securely and safely within membranes (cellular envelopes). These vesicles act as 'postmen' delivering chemical messengers (e.g. cytokines) between cells and are important in various diseases where inflammation is implicated. The investigators have demonstrated that MVs have a fundamental role in the development of organ failure in laboratory models of non-COVID ARDS but the investigators do not yet know the role of these vesicles in the development of ARDS/MOF in COVID-19.
The investigators hypothesise that during COVID-19 infection of the lung, significant numbers of MVs are released within the lung (especially in severe COVID-19), which then "transmit" signals and inflammation to other organs via the bloodstream, causing organs to fail. Furthermore, as chemical messengers (e.g. cytokines) are hidden inside these vesicles, they are not measured by standard laboratory techniques and may explain why there are low cytokine levels in blood. This may also clarify why treatments inhibiting circulating cytokines (not hidden in vesicle membranes) have failed.
To explore these ideas, the group aim to investigate MVs in blood and urine of ICU patients with severe COVID-19 (20mls blood (1 1/3 tablespoons); 10ml urine (3/4 tablespoon)). The investigators intend to examine which chemicals are present in these tiny vesicles and to relate this information to the clinical progress or otherwise of patients. These data will help the scientific community understand the chemical systems involved in severe COVID-19, tell us the significance of MVs and whether blocking MV signalling could lead to new treatments for COVID-19. Furthermore, analysis of these MVs may allow the investigators to identify patients who are likely to become seriously ill, which would help in planning treatment.
- Conditions
- COVID
- Being tested
- no intervention-mechanistic study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no intervention-mechanistic studyOther
no intervention-mechanistic study
| Study group | Role | What they receive |
|---|---|---|
| COVID critically unwell patients | Not described | |
| Non-Covid critically unwell Patietns | Not described Receives: Other: no intervention-mechanistic study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19
This will involve measurement of microvesicles in blood (numbers of MVs per µL)
Measured: 18 months
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19
This will involve measurement of microvesicles in bronchoalveolar lavage fluid (numbers of MVs per µL)
Measured: 18 months
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19
This will involve measurement of microvesicles in urine (numbers of MVs per µL)
Measured: 18 months
Secondary outcomes (3)
Correlation of inflammatory mediators in the bronchoalveolar lavage fluid with extent of lung injury (e.g. based upon oxygen requirement)
The aforementioned inflammatory markers will be correlated with level fo lung injury which will be based upon the level of oxygen required by patients. (numbers of MVs per µL)
Measured: 18 months
Correlation of circulating inflammatory mediators with renal and cardiovascular markers
The aforementioned inflammatory markers will be measured in renal outcomes (creatinine and urine output) and cardiovascular markers (e.g. natriuretic peptides (BNP and NT pro-BNP) and Troponin). (numbers of MVs per µL)
Measured: 18 months
Assess the role of inflammatory mediators obtained from patients in the development of renal injury using in vitro
models (i.e. applying these inflammatory mediators isolated from these clinical samples on kidneys cells in a petri dish) (numbers of MVs per µL)
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2020
- Study start1 Jun 2020
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVIDStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04399603
- Sponsor's protocol ID
- 283783
- Status last verified
- Mar 2024
- First submitted
- 19 May 2020
- Last updated
- 8 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-organ Failure in SARS-CoV2: Identifying Mechanisms and Potential Therapeutic Targets
- ClinicalTrials.gov ID
- NCT04399603
- Acronym / sponsor ID
- 283783
- Conditions
- COVID
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 22 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the United Kingdom, there are currently 138,000 confirmed patients with coronavirus, causing 18,738 deaths. Whilst the disease may be mild in the majority of patients, a significant proportion of patients require intensive care therapy and a ventilator due to lung injury. In addition to lung injury/failure (acute respiratory distress syndrome (ARDS)), around 50% of patients admitted to intensive care develop acute kidney injury (AKI) (requiring advanced support via haemofiltration) and multi-organ failure.
It is unclear why patients suffering from COVID-19 develop such severe lung injury (requiring life support or ventilation) or indeed why patients develop other organ dysfunction such as kidney injury. The investigators hypothesis that this may due to an over-reaction of the immune system particularly in the lungs. This then results in the release of various mediators and biological messengers which can be pushed into the blood bloodstream (exacerbated by positive pressure generated by the ventilator). These mediators then travel, via the blood, to other organs such as the kidney where they cause inflammation and injury of cells, resulting in organ failure.
The investigators would like to apply their well-established laboratory methods to further the scientific community's knowledge of this severe and deadly viral condition and we hope that this would lead to the development of medication that would treat this deadly virus.
Detailed description
COVID-19 is a highly contagious virus, causing a global health emergency. A significant number (~17%) of hospitalised patients become severely unwell and require admission to an intensive care unit (ICU) due to lung failure (acute respiratory distress syndrome (ARDS)) and multi-organ failure (MOF). Sadly, 51.8% of COVID-ARDS patients develop kidney failure, which has a markedly increased risk of dying (61%). We have learned that kidney failure starts several days after lung failure, which suggest an initial viral "attack" on the lungs followed by kidney involvement several days later.
Cytokines are "signalling" molecules made by cells, which in healthy individuals help fight disease. It was initially thought that in COVID-19, lung cells release excessive cytokines (i.e. cytokine storm), which then cause kidney injury and MOF. However, research has demonstrated that cytokine levels in blood are actually very low and not enough to explain the extent of organ injury in COVID-19. This perhaps explains why treatment strategies aimed at specifically damping down the action of these particular cytokines in COVID-19 have failed. Consequently, there remains no cure for COVID-19 MOF, and whilst treatments such as steroids, manage symptoms, have a general anti-inflammatory effect and improve mortality, 30% of intensive care patients still die. Therefore, urgent research is needed to improve scientific knowledge of this condition and identify new therapies.
Microvesicles (MVs) are extremely small particles released by cells and carry various chemicals including cytokines, from inside the cell, packaged securely and safely within membranes (cellular envelopes). These vesicles act as 'postmen' delivering chemical messengers (e.g. cytokines) between cells and are important in various diseases where inflammation is implicated. The investigators have demonstrated that MVs have a fundamental role in the development of organ failure in laboratory models of non-COVID ARDS but the investigators do not yet know the role of these vesicles in the development of ARDS/MOF in COVID-19.
The investigators hypothesise that during COVID-19 infection of the lung, significant numbers of MVs are released within the lung (especially in severe COVID-19), which then "transmit" signals and inflammation to other organs via the bloodstream, causing organs to fail. Furthermore, as chemical messengers (e.g. cytokines) are hidden inside these vesicles, they are not measured by standard laboratory techniques and may explain why there are low cytokine levels in blood. This may also clarify why treatments inhibiting circulating cytokines (not hidden in vesicle membranes) have failed.
To explore these ideas, the group aim to investigate MVs in blood and urine of ICU patients with severe COVID-19 (20mls blood (1 1/3 tablespoons); 10ml urine (3/4 tablespoon)). The investigators intend to examine which chemicals are present in these tiny vesicles and to relate this information to the clinical progress or otherwise of patients. These data will help the scientific community understand the chemical systems involved in severe COVID-19, tell us the significance of MVs and whether blocking MV signalling could lead to new treatments for COVID-19. Furthermore, analysis of these MVs may allow the investigators to identify patients who are likely to become seriously ill, which would help in planning treatment.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| COVID critically unwell patients | – | – |
| Non-Covid critically unwell Patietns | – | Other: no intervention-mechanistic study |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Critically unwell patients requiring organ support
Key inclusion criteria (3 listed)
- Male and female patients aged 18-90 years;
- Patients diagnosed with COVID-19 and without COVID-19 (control purposes);
- Patients who have developed evidence of organ injury failure (requiring oxygen).
Key exclusion criteria (4 listed)
- Patients who are under the age of 18;
- Refusal to consent/gain assent;
- Presence of an advanced directive to withhold or to withdraw life-sustaining treatment;
- Moribund patient likely to die within 24 hours.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no intervention-mechanistic studyno intervention-mechanistic study | Other | Non-Covid critically unwell Patietns |
Primary outcome
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19
Time frame: 18 months
This will involve measurement of microvesicles in blood (numbers of MVs per µL)
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19
Time frame: 18 months
This will involve measurement of microvesicles in bronchoalveolar lavage fluid (numbers of MVs per µL)
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19
Time frame: 18 months
This will involve measurement of microvesicles in urine (numbers of MVs per µL)
3 secondary outcomes
Correlation of inflammatory mediators in the bronchoalveolar lavage fluid with extent of lung injury (e.g. based upon oxygen requirement)
Time frame: 18 months
Correlation of circulating inflammatory mediators with renal and cardiovascular markers
Time frame: 18 months
Assess the role of inflammatory mediators obtained from patients in the development of renal injury using in vitro
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chelsea and Westminster Hospital NHS Foundation Trust
London, United Kingdom
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID, run by Imperial College London at 2 sites 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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Variation in inflammatory mediators in patients with multi-organ failure suffering from COVID-19 (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Mar 2024.