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NCT Number: NCT04453527

The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Covid-19

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

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Key information

Conditions

Coronavirus Coronaviridae Infections Coronavirus Infections Infections Nidovirales Infections RNA Virus Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Portsmouth Hospitals NHS Trust

Portsmouth, PO6 3LY, United Kingdom

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 1. Adults ≥18 years old requiring hospital admission for COVID-19
  • 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.

Exclusion criteria

  • 1. Renal replacement therapy on ITU
  • Significant trauma (including an acute fracture or significant head injury)
  • Massive transfusion of blood products
  • 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.

Treatment and study plan

Primary outcomes

  1. Complement Activation

    Time frame: 14 days sampling time period

    C5a, C5, C3, sC5b9, Bb concentration from serum

  2. Leukotrienes Measure

    Time frame: 14 days sampling time period

    LTB4 concentration from plasma

  3. Coagulation Measure

    Time frame: 14 days sampling time period

    Level of platelets, INR, APTS, D-Dimer, Fibrinogen, thrombin antithrombin complex (TAT), from citrate plasma

  4. Hyperinflammation Measure

    Time frame: 14 days sampling time period

    • CRP, Ferritin, PCT, LDH, Troponin, ALT from plasma

  5. Cell Count

    Time frame: 14 days sampling time period

    Total White Blood Cell count (including lymphocytes, monocytes and neutrophils)

  6. 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

  7. Endothelial dysfunction measures:

    Time frame: 14 days sampling time period

    VEGF, tissue factor and PAI-1, from plasma

Sponsors and collaborators

Lead sponsor

Portsmouth Hospitals NHS Trust

Other Gov

Collaborators

  • Akari Therapuetics

Registry information

Official study title

The CASCADE Study - Measures of Complement Activation and Inflammation in Patients With Coronavirus Disease 2019

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Jul 1, 2020
Registry last updated
Apr 7, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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