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

NCT04453527 | Completed

• 1 other identifier: PHT/2020/37
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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 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

Conditions

Coronavirus

Outcome Measures

Primary Outcomes (7)

• Complement Activation

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

  14 days sampling time period

• Leukotrienes Measure

  LTB4 concentration from plasma

  14 days sampling time period

• Coagulation Measure

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

  14 days sampling time period

• Hyperinflammation Measure

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

  14 days sampling time period

• Cell Count

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

  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

  14 days sampling time period

• Endothelial dysfunction measures:

  VEGF, tissue factor and PAI-1, from plasma

  14 days sampling time period

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants with Covid 19 and Healthy Volunteers

You may qualify if:

• \- 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Portsmouth Hospitals NHS Trust: lead
• Akari Therapuetics: collaborator

Study Sites (1)

Portsmouth Hospitals NHS Trust

Portsmouth, PO6 3LY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37731491 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample

MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 1, 2020
• Study Start: May 28, 2020
• Primary Completion: May 30, 2021
• Study Completion: May 30, 2021
• Last Updated: April 7, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)