CoronavirusNCT04453527
The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Covid-19
An observational study of Coronavirus, run by Portsmouth Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
COVID-19 is a new disease and therefore it is still not clear exactly how the virus affects the body and why people are affected so differently. It causes infection in the lungs and the virus can then attack blood vessels in the lungs and other organs to spark off an inflammatory process that can make a person very… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronavirus
- How many people
- 72 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 May 2020to 30 May 2021
- 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 years and older
- All sexes
- Adult, Older adult
Study population: Participants with Covid 19 and Healthy Volunteers
Who may be able to join
- 1. Adults ≥18 years old requiring hospital admission for COVID-19
- 2. COVID-19 confirmed by either:
- A positive swab (using RT-PCR)
- OR based on a high level of clinical probability confirmed by the presence of typical symptoms and compatible radiological findings on imaging with no alternative cause for these findings identified by the treating physician.
Who cannot join
- 1. Renal replacement therapy on ITU
- 2. Significant trauma (including an acute fracture or significant head injury)
- 3. Massive transfusion of blood products
- 4. Confirmed bacteraemia with pathogenic organism on blood cultures or other severe bacterial infections (including abscess/empyema) which persist despite broad-spectrum antibiotics and are thought to be significantly contributing to the patient's symptoms and clinical state. Recruitment will not be delayed however pending a negative culture.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Portsmouth Hospitals NHS Trust
Portsmouth, PO6 3LY
About this study
Official title: The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Coronavirus Disease 2019
COVID-19 is a new disease and therefore it is still not clear exactly how the virus affects the body and why people are affected so differently. It causes infection in the lungs and the virus can then attack blood vessels in the lungs and other organs to spark off an inflammatory process that can make a person very ill. It also can cause damage within tiny blood vessels that makes a person's blood thicken up and stop flow in vital organs. The investigators believe complement (which is a chemical in the body which can be harmful in excess) orchestrates the inflammation and thickening of the blood that can make a person sick. The investigators now need to know which of these complement chemicals are elevated in COVID-19 and compare to healthy volunteers, and assess whether the levels are higher in people with severe lung disease. The investigators believe that if levels are increased there are special treatments that can counteract them and potentially be an effective treatment for COVID-19.
In this study the investigators will measure different parts of the inflammation process to better understand what may be causing severe disease and to see if there may be benefits from a new treatment to reduce inflammation
Read the detailed description
This study is an observational cross-sectional and cohort study to assess whether there is evidence of increased complement activation and/or LTB4 levels and other parameters of inflammation and a pro-coagulative state in adult patients hospitalised with COVID-19 compared to healthy controls and also whether these measures differ with increasing severity of respiratory failure.
Blood samples (serum and plasma) will be obtained from each participant at the time of recruitment into the trial, to assess the profile of complement activation, cytokines/ chemokines, leukotrienes (specifically leukotriene B4) and markers of coagulation and inflammation in patients with COVID-19.
Participants within the cohort study will be recruited at the point of admission or as close to it as possible. Baseline sampling will be performed at time of recruitment. There will be up to 2 additional sampling points (with not more than one sample per day) if there is any worsening of the participants respiratory failure (i.e. deteriorating from mild to moderate or moderate to severe disease).
Patients just admitted to hospital will be asked to consent for both the case control and the cohort study
Data will be collected at baseline for all participants and then again at each further sampling point for the participants within the cohort study.
Patient status will be measured at 14 days from the last point of sampling.
- Conditions
- Coronavirus
- Medical subject headings
- Coronavirus Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
Complement Activation
C5a, C5, C3, sC5b9, Bb concentration from serum
Measured: 14 days sampling time period
Leukotrienes Measure
LTB4 concentration from plasma
Measured: 14 days sampling time period
Coagulation Measure
Level of platelets, INR, APTS, D-Dimer, Fibrinogen, thrombin antithrombin complex (TAT), from citrate plasma
Measured: 14 days sampling time period
Hyperinflammation Measure
- CRP, Ferritin, PCT, LDH, Troponin, ALT from plasma
Measured: 14 days sampling time period
Cell Count
Total White Blood Cell count (including lymphocytes, monocytes and neutrophils)
Measured: 14 days sampling time period
Cytokines and Chemokine Measure
Level of • Pro-inflammatory - IL-1α, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-17, GCSF, GMCSF, IFN γ, IP10, MCP-1, MIP1α, TNFα and anti inflammatory IL-4, IL-10, IL-13, IL-22, TGF-α from plasma
Measured: 14 days sampling time period
Endothelial dysfunction measures:
VEGF, tissue factor and PAI-1, from plasma
Measured: 14 days sampling time period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2020
- Study start28 May 2020
- Primary completion30 May 2021
- Study completion30 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CoronavirusStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Portsmouth Hospitals NHS Trust
- Sponsor type
- Other government
- Collaborators
- Akari Therapuetics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04453527
- Sponsor's protocol ID
- PHT/2020/37
- Status last verified
- Apr 2023
- First submitted
- 25 Jun 2020
- Last updated
- 7 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wiffen L, D'Cruz LG, Brown T, Higenbottam TW, Bernstein JA, Campbell C, Moellman J, Ghosh D, Richardson C, Weston-Davies W, Chauhan AJ. Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning. Front Immunol. 2023 Sep 5;14:1192765. doi: 10.3389/fimmu.2023.1192765. eCollection 2023.
PubMed 37731491
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Coronavirus Disease 2019
- ClinicalTrials.gov ID
- NCT04453527
- Acronym / sponsor ID
- PHT/2020/37
- Conditions
- Coronavirus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Portsmouth Hospitals NHS TrustOther government
- Collaborators
- Akari Therapuetics
- Study start
- 28 May 2020 (actual)
- Primary completion
- 30 May 2021 (actual)
- Study completion
- 30 May 2021 (actual)
- First posted
- 1 Jul 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.
COVID-19 is a new disease and therefore it is still not clear exactly how the virus affects the body and why people are affected so differently. It causes infection in the lungs and the virus can then attack blood vessels in the lungs and other organs to spark off an inflammatory process that can make a person very ill. It also can cause damage within tiny blood vessels that makes a person's blood thicken up and stop flow in vital organs. The investigators believe complement (which is a chemical in the body which can be harmful in excess) orchestrates the inflammation and thickening of the blood that can make a person sick. The investigators now need to know which of these complement chemicals are elevated in COVID-19 and compare to healthy volunteers, and assess whether the levels are higher in people with severe lung disease. The investigators believe that if levels are increased there are special treatments that can counteract them and potentially be an effective treatment for COVID-19.
In this study the investigators will measure different parts of the inflammation process to better understand what may be causing severe disease and to see if there may be benefits from a new treatment to reduce inflammation
Detailed description
This study is an observational cross-sectional and cohort study to assess whether there is evidence of increased complement activation and/or LTB4 levels and other parameters of inflammation and a pro-coagulative state in adult patients hospitalised with COVID-19 compared to healthy controls and also whether these measures differ with increasing severity of respiratory failure.
Blood samples (serum and plasma) will be obtained from each participant at the time of recruitment into the trial, to assess the profile of complement activation, cytokines/ chemokines, leukotrienes (specifically leukotriene B4) and markers of coagulation and inflammation in patients with COVID-19.
Participants within the cohort study will be recruited at the point of admission or as close to it as possible. Baseline sampling will be performed at time of recruitment. There will be up to 2 additional sampling points (with not more than one sample per day) if there is any worsening of the participants respiratory failure (i.e. deteriorating from mild to moderate or moderate to severe disease).
Patients just admitted to hospital will be asked to consent for both the case control and the cohort study
Data will be collected at baseline for all participants and then again at each further sampling point for the participants within the cohort study.
Patient status will be measured at 14 days from the last point of sampling.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Participants with Covid 19 and Healthy Volunteers
Key inclusion criteria (4 listed)
- 1. Adults ≥18 years old requiring hospital admission for COVID-19
- A positive swab (using RT-PCR)
- OR based on a high level of clinical probability confirmed by the presence of typical symptoms and compatible radiological findings on imaging with no alternative cause for these findings identified by the treating physician.
Key exclusion criteria (4 listed)
- 1. Renal replacement therapy on ITU
- 2. Significant trauma (including an acute fracture or significant head injury)
- 3. Massive transfusion of blood products
- 4. Confirmed bacteraemia with pathogenic organism on blood cultures or other severe bacterial infections (including abscess/empyema) which persist despite broad-spectrum antibiotics and are thought to be significantly contributing to the patient's symptoms and clinical state. Recruitment will not be delayed however pending a negative culture.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Complement Activation
Time frame: 14 days sampling time period
C5a, C5, C3, sC5b9, Bb concentration from serum
Leukotrienes Measure
Time frame: 14 days sampling time period
LTB4 concentration from plasma
Coagulation Measure
Time frame: 14 days sampling time period
Level of platelets, INR, APTS, D-Dimer, Fibrinogen, thrombin antithrombin complex (TAT), from citrate plasma
Hyperinflammation Measure
Time frame: 14 days sampling time period
• CRP, Ferritin, PCT, LDH, Troponin, ALT from plasma
Cell Count
Time frame: 14 days sampling time period
Total White Blood Cell count (including lymphocytes, monocytes and neutrophils)
Cytokines and Chemokine Measure
Time frame: 14 days sampling time period
Level of • Pro-inflammatory - IL-1α, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-17, GCSF, GMCSF, IFN γ, IP10, MCP-1, MIP1α, TNFα and anti inflammatory IL-4, IL-10, IL-13, IL-22, TGF-α from plasma
Endothelial dysfunction measures:
Time frame: 14 days sampling time period
VEGF, tissue factor and PAI-1, from plasma
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
- Derived from this study: PubMed 37731491Wiffen L, D'Cruz LG, Brown T, Higenbottam TW, Bernstein JA, Campbell C, Moellman J, Ghosh D, Richardson C, Weston-Davies W, Chauhan AJ. Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning. Front Immunol. 2023 Sep 5;14:1192765. doi: 10.3389/fimmu.2023.1192765. eCollection 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronavirus, run by Portsmouth Hospitals NHS Trust 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 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: finished, as of the sponsor's last update on 7 Apr 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Complement Activation (time frame: 14 days sampling time period). The study lists 7 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 NCT04453527, which also lists 1 linked publication.
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 7 Apr 2023.