ASTERIX: An observational study to identify sub-groups of COVID-19 patients based on their demographic, clinical and laboratory profile, and to determine if these sub-groups can be used to predict severity of disease and response to therapy

ISRCTN	ISRCTN66141262
DOI	https://doi.org/10.1186/ISRCTN66141262
IRAS number	283989
Secondary identifying numbers	CPMS 46231, IRAS 283989

Submission date: 09/09/2020
Registration date: 22/10/2020
Last edited: 19/05/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Background and study aims
The new coronavirus disease, SARS-CoV-2, is a rapidly emerging global health threat. Health care systems have been on the brink of collapse across the world, reflecting the absence of effective treatment for severe coronavirus 19 disease (COVID-19). Early data show marked differences in the extent to which patients are affected by the virus, with 80% showing little or no symptoms, while others have severe disease, with a fatality rate of 1-2%, usually as the result of progressive COVID pneumonia. The disease can affect people very differently and this study wishes to identify sub-groups of patients to allow targeting of treatment for maximum impact and minimum risk, ideally using biological signatures, or ‘endotypes’. ASTERIX is an observational study that will collect surplus samples (blood, respiratory secretions and urine) and data on COVID patients admitted to hospital. This study aims to identify and define these sub-groups of patients, and demonstrate the link between endotype and severity of disease and likely response to treatment.

Who can participate?
All patients 8 years and over admitted to hospital with suspected COVID-19 are eligible to participate.

What does the study involve?
There are no specific trial activities. Patients will be asked to give consent verbally to have their clinical data collected, and for any surplus samples of blood, respiratory secretions, and urine collected during admission and up to 1 year afterward to be available for research purposes.

What are the possible benefits and risks of participating?
There is no direct benefit to the patient, however, the data collected may provide information that can improve future care for COVID-19 patients.

Where is the study run from?
The study is co-ordinated by the CRUK Clinical Trials Unit (UK), and is sponsored by NHS Greater Glasgow and Clyde (UK).

When is the study starting and how long is it expected to run for?
The study will run from April 2020 to January 2022 (updated 21/06/2022, previously: April 2021; updated 05/01/2021, previously: January 2021). Data have been collected retrospectively from January 2020, and patients will continue to be recruited until January 2021.

Who is funding the study?
Chief Scientist Office, Scottish Government (UK) and the National Institute for Health Research (UK)

Who is the main contact?
1. Professor Kevin Blyth (CI)
Kevin.Blyth@glasgow.ac.uk
2. Mrs Carol Evans
carol.evans@glasgow.ac.uk

Contact information

Mrs Carol Evans
Scientific

Clinical Trials Unit
Level 0, Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom

Phone	+44 (0)141 301 7189
Email	carol.evans@glasgow.ac.uk

Study information

Study design	Observational cohort trial
Primary study design	Observational
Secondary study design	Cohort study
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	No participant information sheet available
Scientific title	Adaptive Stratification of COVID-19 to facilitate Endotype-directed Intervention Studies (ASTERIX)
Study acronym	ASTERIX
Study hypothesis	That it is possible to identify discrete sub-groups of patients (endotypes), based on a range of demographic, clinical, and laboratory biomarkers, that predict: 1. Progression though different stages of disease severity 2. The likelihood of response to therapies
Ethics approval(s)	Approved 21/05/2020, West of Scotland REC 5 (West of Scotland Research Ethics Service, Ward 11, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE; +44 (0)141 314 0213; WoSREC5@ggc.scot.nhs.uk), ref: 20/WS/0077
Condition	COVID-19 (SARS-CoV-2 infection)
Intervention	The study aims to achieve the following: 1. Recruit between 600 and 1200 participants with appropriate approvals 2. To acquire and record the necessary biological and outcome data using direct electronic medical record (EMR) capture and a bespoke data collection tool embedded in COVID19 clinical care (the NHS GGC COVID19 assessment tool). 3. Provide a structured biobanking infrastructure, with surplus biological samples linked to clinical data, and a resource for observational, translational and interventional studies 4. Develop different statistical models based on the data collected for progression to three adverse outcomes: 4.1. COVID-19 Pneumonia 4.2. Development of respiratory failure, sufficient to prompt escalation to at least Step 6 of the World Health Organisation (WHO) 10-point ordinal scale 4.3. Death from any cause These models will generate critical information needed to design high impact clinical trials, including the most suitable mechanism(s) of action at different phases of the illness and the event rate at each timepoint based on current standard of care. Data Collection Data will be extracted from clinical record into the NHS GG&C Safe Haven. Automated processes will capture most data fields. However, daily clinical data (e.g. oxygen requirement, clinical observations, vital status) will be collected by ward staff, using a bespoke bedside data collection tool embedded in clinical care (the NHSGGC COVID19 assessment tool). This information will constitute the routine clinical record therefore no study visits will be required. Biological Sample Processing and Banking No study specific blood samples will be taken. Surplus blood (+/- any surplus respiratory secretions and urine) will be collected from the laboratories at Baseline (Day 0) and where possible in a series of follow-up windows that span the course of admission (up to 14 days). If blood samples are sent from any hospital follow-up visit within 1-year these will also be banked. Immediate blood sample processing will allow storage of plasma, serum and Peripheral Blood Mononuclear Cells (PBMCs) for COVID research. Statistical Analyses The target sample size of 600-1200 will yield 400-800 confirmed cases. These numbers will be sufficient for the primary statistical analyses (generation of reliable models for each progression event). The content of these models will include the routinely available clinical data, the result of blood test performed in clinical practice and the results of a limited number of additional tests performed on the surplus blood samples. These additional assays will include measurements implicated in COVID-19 series, but not routinely measured by clinical teams (e.g. Troponin, D-Dimer). Multivariable predictive models (endotypes) will be generated for each progression event using logistic regression, and the performance of any developed models will be validated in an independent data set.
Intervention type	Other
Primary outcome measure	To acquire and record the necessary biological and outcome data by extracting electronic medical records held by the NHS trust Safe Haven, collected at various timepoints by automated processes. Daily clinical data (e.g. oxygen requirement, clinical observations, vital status) will also be collected by ward staff using a bedside clinical collection tool embedded in clinical care daily clinical data (the NHSGGC COVID19 assessment tool). Biological materials (e.g. blood, respiratory secretions, urine) for potential translational research will be surplus material from that routinely collected during the hospital admission, and also any follow-up hospital visits within 1 year.
Secondary outcome measures	There are no secondary outcome measures
Overall study start date	01/04/2020
Overall study end date	31/01/2022

Eligibility

Participant type(s)	Patient
Age group	Mixed
Sex	Both
Target number of participants	Planned Sample Size: 600; UK Sample Size: 600
Total final enrolment	6000
Participant inclusion criteria	1. Admitted to hospital with suspected COVID-19
Participant exclusion criteria	1. Aged <8 years (lower age limit aligns with current NHSGGC Biorepository REC approval for storage and use of surplus tissue)
Recruitment start date	01/01/2020
Recruitment end date	30/01/2021

Locations

Countries of recruitment

Scotland
United Kingdom

Study participating centre

NHS Greater Glasgow and Clyde

J B Russell House Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom

Sponsor information

NHS Greater Glasgow and Clyde
Hospital/treatment centre

Reay House
17 Old Edinburgh Road
Inverness
G12 0XH
Scotland
United Kingdom

Phone	+44 (0)14713144001
Email	joanne.mcgarry@ggc.scot.nhs.uk
Website	http://www.nhsggc.org.uk/
"ROR"	https://ror.org/05kdz4d87

Funders

Funder type

Government

Chief Scientist Office, Scottish Government Health and Social Care Directorate
Government organisation / Local government

Alternative name(s): Chief Scientist Office, Scottish Government Health Directorate CSO, Chief Scientist Office, Scottish Government Health Directorates, Chief Scientist Office of the Scottish Government Health Directorates, Scottish Government Health and Social Care Directorate of the Chief Scientist Office, Scottish Government Health Directorate Chief Scientist Office, The Chief Scientist Office, CSO
Location: United Kingdom

National Institute for Health Research (NIHR) (UK)
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	31/10/2023
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer reviewed journal estimated December 2021.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from NHSGGC safe haven (safehaven@ggc.scot.nhs.uk). The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version v1.0	11/05/2020	05/11/2020	No	No
HRA research summary			28/06/2023	No	No

Additional files

ISRCTN66141262_PROTOCOL_v1.0_11May2020.pdf: uploaded 05/11/2020

Editorial Notes

19/05/2023: The intention to publish date has been changed from 31/10/2022 to 31/10/2023.
21/06/2022: The following changes have been made:
1. The total final enrolment number has been added.
2. The overall trial end date has been changed from 30/04/2021 to 31/01/2022 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 01/12/2021 to 31/10/2022.
12/08/2021: Internal review.
19/03/2021: Internal review.
05/01/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/01/2021 to 30/01/2021.
2. The overall end date was changed from 01/01/2021 to 30/04/2021.
3. The plain English summary was updated to reflect these changes.
05/11/2020: Uploaded protocol (not peer reviewed) Version 1, 11 May 2020.
09/09/2020: Trial’s existence confirmed by the National Institute for Health Research (NIHR).