Condition category
Infections and Infestations
Date applied
12/05/2020
Date assigned
20/05/2020
Last edited
20/05/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of April 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
Hospitals are recognised to be a major risk for the spread of infections despite the availability of protective measures. Under normal circumstances, staff may acquire and transmit infections, but the health impact of within hospital infection is greatest in vulnerable patients. For the novel coronavirus that causes COVID-19, like recent outbreaks such as the SARS and Ebola virus, the risk of within hospital spread of infection presents an additional, significant health risk to healthcare workers. Infection Prevention and Control (IPC) teams within hospitals engage in practices that minimise the number of infections acquired within hospital. This includes surveillance of infection spread, and proactively leading on training to clinical and other hospital teams. There is now good evidence that genome sequencing of epidemic viruses such as that which causes COVID-19, together with standard IPC, more effectively reduces within hospital infection rates and may help identify the routes of transmission, than just existing IPC practice. The aims of the study are to evaluate the benefit of genome sequencing in this context, and whether rapid (24-48 hour) turnaround on the data to IPC teams has an impact on that level of benefit.

Who can participate?
Inpatients who are COVID-19 positive and suspected of having been transmitted the virus from the hospital setting (where positive over 48 hours after admission)

What does the study involve?
The study involves the use of genomic sequencing of COVID-19-positive patients in hospitals to inform Infection Prevention Control (IPC) measures undertaken within the hospital in the hopes of reducing hospital transmission of the virus. The study team will ask participating NHS hospitals to collect IPC information as per usual practice for a short time to establish data for comparison. Where patients are confirmed to have a COVID-19 infection thought to have been transmitted within hospital, their samples will be sequenced with data fed back to hospital teams during the intervention phase. A final phase without the intervention may take place for additional information on standard IPC practice when the COVID-19 outbreak is at a low level nationwide.

What are the possible benefits and risks of participating?
Any participants in this study will already have confirmed COVID-19 infection. Therefore any benefits to these patients of the intervention will be indirect. The potential benefit to the participants will be dependent on the effectiveness of the intervention and their location within the hospital. In the event the intervention results in a lower level of nosocomial transmissions, it is likely that participants will benefit from lower numbers than otherwise of COVID-19 cases at the NHS site, and therefore more staffing resource on a per participant basis being available. The substantive overarching benefit of proven effectiveness for this study would be for patients generally within the hospital setting, and potentially the wider public. There are no anticipated risks to participation beyond having confirmed COVID-19 infection.

Where is the study run from?
University College London (UCL)

When is the study starting and how long is it expected to run for?
March 2020 to April 2021

Who is funding the study?
COG-UK Consortium (UK)

Who is the main contact?
Unfortunately, this study is not recruiting public volunteers at this time. Please do not contact the research team as they will not be able to respond. For more information about COVID-19 research, visit the Be Part of Research homepage.

Trial website

https://www.cogconsortium.uk/studies

Contact information

Type

Public

Primary contact

Mr James Blackstone

ORCID ID

Contact details

Comprehensive Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
90 High Holborn 2nd Floor
London
WC1V 6LJ
United Kingdom
+44 (0)203 108 6584
cctu.hoci@ucl.ac.uk

Type

Scientific

Additional contact

Prof Judith Breuer

ORCID ID

Contact details

University College London
Division of Infection and Immunity
Gower Street
London
WC1E 6BT
United Kingdom
+44 (0)20 3108 2130
cctu.hoci@ucl.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CTU/2020/353, IRAS 283014

Study information

Scientific title

A Phase III prospective, interventional, cohort, superiority study to evaluate the benefit of rapid COVID-19 genomic sequencing (the COVID-19 GENOMICS UK Project) on infection control in preventing the spread of the virus in UK NHS hospitals

Acronym

COG-UK HOCI

Study hypothesis

Hospitals are recognised to be a major risk for the spread of infections despite the availability of protective measures. Under normal circumstances, staff may acquire and transmit infections, but the health impact of within hospital infection is greatest in vulnerable patients. For the novel coronavirus that causes COVID-19, like recent outbreaks such as the SARS and Ebola virus infections, the risk of within-hospital spread of infection presents an additional, significant health risk to healthcare workers.

Infection Prevention and Control (IPC) teams within hospitals engage in practices that minimise the number of infections acquired within hospital. This includes surveillance of infection spread, and proactively leading on training to clinical and other hospital teams.

There is now good evidence that genome sequencing of epidemic viruses such as that which causes COVID-19, together with standard IPC, more effectively reduces within-hospital infection rates and may help identify the routes of transmission, than just existing IPC practice. It is proposed to evaluate the benefit of genome sequencing in this context, and whether rapid (24-48 h) turnaround on the data to IPC teams has an impact on that level of benefit.

The study team will ask participating NHS hospitals to collect IPC information as per usual practice for a short time to establish data for comparison. Where patients are confirmed to have a COVID-19 infection thought to have been transmitted within the hospital, their samples will be sequenced with data fed back to hospital teams during the intervention phase. A final phase without the intervention may take place for additional information on standard IPC practice when the COVID-19 outbreak is at a low level nationwide.

Ethics approval

Approved 23/04/2020, East of England - Cambridge South Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 104 8065; cambridgesouth.rec@hra.nhs.uk), ref: 20/EE/0118

Study design

Phase III prospective interventional cohort superiority study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not applicable

Condition

Hospital-onset COVID-19 (SARS-CoV-2 infection)

Intervention

Allocation to either rapid local sequencing (c. 24-48 h) or lack of rapid local sequencing (i.e. via Wellcome Sanger Institute at >96 h) will be dependent on the time of the study (see below). All sites will perform both rapid and standard sequencing in sequentially.

Proposed study duration: 12 months; comprising 6 months of set-up, baseline data collection, interventional data collection) and up to 6 months of data cleaning, data analysis and reporting.

Study intervention: Genomic-sequence informed IPC measures: Use of virus (COVID-19) genome sequence report to inform infection prevention control procedures. Rapid or standard (time to return to sites) receipt of virus (COVID-19) genomic sequencing reports.

1. Baseline/control phase 1
Sample collection and genomic sequencing from COVID-19 positive participants suspected of acquiring infection in hospital (suspected nosocomial COVID-19 infection where tested positive >48 h after hospital admission) where sequencing reports are not received by Infection Prevention Control (IPC) site teams.

2. Site intervention phase
Sample collection and genomic sequencing from COVID-19 positive participants suspected of acquiring infection in hospital where sequencing reports generated both rapid or standard and received by site IPC teams for interpretation and action.

3. Control phase 2
Sample collection and genomic sequencing from COVID-19 positive participants suspected of acquiring infection in hospital where sequencing reports not interpreted/actioned by IPC site teams - where deemed ethical and approved by oversight committee.

Cohort follow baseline (no report receipt), then rapid vs standard sequencing report receipt phase, then return to baseline phase (no report receipt).

Proposed study duration: 12 months total; comprising 6 months of set-up, baseline data collection, interventional data collection) and up to 6 months of data cleaning, data analysis and reporting.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Incidence rate of IPC-defined HOCIs, measured as incidence rate of recorded cases per week per 100 inpatients based on case report forms during each phase of the study
2. Identification of nosocomial transmission using sequencing data in potential HOCIs in whom this was not identified by pre-sequencing IPC evaluation, measured using pre- and post-sequencing case report forms for each enrolled patient during study phases in which the sequence reporting tool is in use

Secondary outcome measures

1. Incidence rate of IPC-defined hospital outbreaks, defined as cases of hospital transmission linked by location and with intervals between diagnoses of no greater than 2 weeks (relevant data extracted from case report forms), measured as incidence rate of outbreak events per week per 100 inpatients during each phase of the study
2. Incidence rate of IPC+sequencing-defined hospital outbreaks, defined by retrospective review of all available sequencing and epidemiological data for identification of transmission clusters and measured as outbreak events per week per 100 inpatients during each phase of the study
3. Changes to IPC actions implemented following receipt of viral sequence report, measured using pre- and post-sequencing case report forms for each enrolled patient during study phases in which the sequence reporting tool is in use
4. Changes to IPC actions that would ideally have been implemented (given unlimited resources) following receipt of viral sequence report, measured using pre- and post-sequencing case report forms for each enrolled patient during study phases in which the sequence reporting tool is in use
5. Health economic benefit of standard and rapid sequencing reports to IPC measured using bespoke health economic case report data comparison between baseline, standard and rapid sequencing phases
6. Number of HCW days off work measured from sampling these data points on case report forms at all study phases

Overall trial start date

17/03/2020

Overall trial end date

30/04/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Participants must have confirmed COVID-19 infection and either:
1.1. Be a potential hospital-onset COVID-19 infection (HOCI), or
1.2. Potential workplace infection with SARS CoV-2 for site-based healthcare workers
2. Participants must have provided nasal swab/pharyngeal swab/combined nasal and pharyngeal swab/nasopharyngeal aspirate or bronchoalveolar lavage sample for evaluation in the COG-UK project.
3. Participants may be of any age or gender to be included in study For clarity, in the above criterion a potential HOCI is an admitted patient at site with first confirmed test for COVID-19 >48 h after admission, where they were not suspected to have COVID-19 at time of admission

Participant type

Patient

Age group

All

Gender

Both

Target number of participants

2000

Participant exclusion criteria

Does not meet inclusion criteria

Recruitment start date

01/06/2020

Recruitment end date

01/10/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
The Bays, St Mary's Hospital South Wharf Road
London
W2 1BL
United Kingdom

Trial participating centre

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

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
Northern General Hospital Herries Road Sheffield
Sheffield
S5 7AU
United Kingdom

Trial participating centre

Guys and St Thomas NHS Foundation Trust
4th Floor, Gassiot House St Thomas Hospital Westminster Bridge Road
London
SE1 7EH
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Comprehensive Clinical Trials Unit
Gower Street
London
WC1E 6BT
United Kingdom
+44 (0)203 108 6584
cctu.hoci@ucl.ac.uk

Sponsor type

University/education

Website

http://www.ucl.ac.uk/

Funders

Funder type

Research organisation

Funder name

COG-UK Consortium

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Protocol and protocol paper will be uploaded as soon as available. Study results will be published in peer-reviewed scientific journals, in internal reports and submitted to regulatory authorities. The researchers will not publish identifiable data - anonymity will be maintained.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date (due to the requirement for further legal clarity in relation to the upcoming expiry of the COPI notice with regards to the trial team’s obligations under the United Kingdom data protection regulation).

Intention to publish date

30/04/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

12/05/2020: Trial's existence confirmed by the NIHR.