Evaluating the influence of abnormalities in immunity due to an extreme reaction to an infection (sepsis) on antibiotic use in critically ill patients
| ISRCTN | ISRCTN86837685 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN86837685 |
| IRAS number | 209815 |
| Secondary identifying numbers | R121074, IRAS 209815, CPMS 45252, NIHR128374 |
- Submission date
- 08/12/2020
- Registration date
- 05/01/2021
- Last edited
- 27/04/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Sepsis is a life threatening condition due to infection in which the immune system has an abnormally over-active and under-active response (immunosuppression). Patients who have pronounced immunosuppression have a higher risk of getting further infections while in hospital, have a longer stay in hospital and even have a higher rate of death.
Patients with sepsis require treatment with antibiotics and the length of antibiotic course is often fixed. A trial (called ADAPT-sepsis https://www.isrctn.com/ISRCTN47473244) is currently underway to see whether two markers that can be measured in blood or ‘biomarkers’ (called procalcitonin (PCT) and c-reactive protein (CRP)), can reduce antibiotic use in patients with sepsis. The purpose is to see if using these biomarkers will reduce antibiotic use. These biomarkers are generally high at the start of the illness and when they fall to a certain level, the clinician will be advised to stop antibiotics.
Who can participate?
Patients enrolled in the ADAPT-sepsis trial.
What does the study involve?
As an observational study, participants will have four blood samples taken over a one-week period. These samples will be sent to a central laboratory for testing of white cell markers which will give a picture of immune function of patients. This observational study is a sub-study of an ongoing randomised controlled trial (ISRCTN47473244) and so all other procedures such as consent and clinical data collection will occur as part of the main trial.
What are the possible benefits and risks of participating?
Individual patients are unlikely to benefit from participating in this study. The amount of additional blood taken is small and is taken in most cases from an arterial or venous tube at the same time as blood required for routine clinical care. In exceptional cases, blood sampling is from a vein using a needle. There may be a sharp scratch when the needle is inserted and possible bruising from the area from which the blood is taken.
Where is the study run from?
The Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
August 2020 to July 2024
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Dr Tom Ewen, Tom.Ewen@newcastle.ac.uk
Dr Thomas Hellyer, thomas.hellyer@newcastle.ac.uk
Contact information
Public
Research Project Managers
Faculty of Medical Sciences
Newcastle University
Newcastle upon Tyne
NE2 4HH
United Kingdom
| Phone | +44 (0)191 208 5644 |
|---|---|
| Tom.Ewen@newcastle.ac.uk |
Scientific
Institute of Cellular Medicine
Newcastle University
Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom
 ORCID ID |
0000-0001-5346-7411 |
|---|---|
| Phone | +44 (0)191 20 82422 |
| thomas.hellyer@newcastle.ac.uk |
Study information
| Study design | Prospective multi-centre exploratory cohort observational study embedded within the ADAPT-sepsis trial |
|---|---|
| Primary study design | Observational |
| Secondary study design | Clinical laboratory |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | https://warwick.ac.uk/fac/sci/med/research/ctu/trials/adaptsepsis/health/isf/ |
| Scientific title | The Role of Immunosuppression in an antibiotic Stewardship intervention and its association with Clinical outcomes and antibiotic use: RISC-sepsis |
| Study acronym | RISC-sepsis |
| Study objectives | As a mechanistic study embedded within a biomarker-guided antibiotic duration trial, this study will determine whether patients with sepsis-induced immunosuppression have prolonged duration of antibiotics and different trial outcomes. |
| Ethics approval(s) | Approved 21/10/2020, South Central - Oxford C Research Ethics Committee (Level 3, Block B, Whitefriars Building, Lewins Mead, Bristol, BS1 2NT, UK; Tel: +44 (0)207 104 8379; oxfordc.rec@hra.nhs.uk), ref: 17/SC/0434 |
| Health condition(s) or problem(s) studied | Hospitalised adults who have been commenced on intravenous antibiotics for sepsis |
| Intervention | As an observational study, participant involvement will be limited to sampling of blood at 4 time points over a one-week period. Blood samples will be transferred to a central laboratory. Immune phenotype will be performed by measuring cellular surface markers by fluorescence-based flow cytometry. These markers will include but not limited to, HLA-DR, CD88, PD-1 and regulatory T cells. ADAPT-sepsis study registration: https://www.isrctn.com/ISRCTN47473244 |
| Intervention type | Other |
| Primary outcome measure | Immune phenotype measured using fluorescence-based flow cytometry of blood samples taken at ... 1. Monocyte HLA-DR 2. Neutrophil CD88 3. T cell, monocyte and neutrophil CD279 4. Percentage of regulatory T cells |
| Secondary outcome measures | Measured using patient records: 1. Total duration of antibiotic treatment to 28 days following randomisation (superiority) measured in days (24-hour time periods) 2. Antibiotic dose, measured as Defined Daily Dose to 28 days 3. Unscheduled care escalation/re-admission 4. Infection relapse/recurrence requiring further antibiotic treatment 5. Super-infection, defined as new infection at a different anatomical site 6. Suspected antibiotic adverse reactions 7. Time to ‘fit’ for hospital discharge |
| Overall study start date | 01/08/2020 |
| Completion date | 31/07/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 198 |
| Total final enrolment | 198 |
| Key inclusion criteria | Patients enrolled in the ADAPT-sepsis trial. Patients are eligible if: 1. Hospitalised adult patients at least 18 years of age 2. Up to 24 hours of initiation of empiric intravenous antibiotic treatments for suspicion of sepsis 3. Likely to remain hospitalised and receiving intravenous antibiotic treatment for at least the next 72 hours 4. Requirement for critical care |
| Key exclusion criteria | 1. More than 24 hours since receiving first empiric intravenous antibiotic treatments for a suspicion of sepsis 2. Prolonged (greater than 21 days) antimicrobial therapy mandated (e.g. for endocarditis, cerebral/hepatic abscess, tuberculosis, osteomyelitis) 3. Severely immunocompromised (e.g. neutropenia, less than 500 neutrophils/microlitre) 4. All treatment for suspected sepsis likely to be stopped within 24 hours of its initiation because of futility 5. Consent declined 6. Previously enrolled in ADAPT-sepsis |
| Date of first enrolment | 01/04/2022 |
| Date of final enrolment | 21/04/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
Sponsor information
University/education
Directorate of Research and Business Engagement
Christie Building
Manchester
M13 9PL
England
United Kingdom
| Phone | +44 (0)161 275 2725 |
|---|---|
| clinicaltrials@manchester.ac.uk | |
| Website | https://www.manchester.ac.uk/ |
"ROR" |
https://ror.org/027m9bs27 |
Funders
Funder type
Government
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 | 31/07/2025 |
|---|---|
| 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. |
| IPD sharing plan | Current IPD sharing statement as of 20/04/2021: Following publication of the study’s findings, publicly available summary data of immune phenotyping datasets will be made findable through those publications. Access to the full dataset will be made available via request to the chief investigator, Dr Tom Hellyer (thomas.hellyer@newcastle.ac.uk). Access requests will be considered in accordance with Newcastle University Data Sharing Policies and all external users submitting applications for access to data will require data sharing agreements in keeping with the NIHR requirements. The data use agreement must detail the agreed use and appropriate management of the data and include a requirement for recognition of the contribution of the researchers who generated the data and the original funder. Patient will consent to archiving of data and data sharing limited to researchers for future research. All data will be available for peer review at the point of deposition and publication, and will be archived for a minimum of 10 years after publication. Previous IPD sharing statement: All data generated or analysed 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 article | 09/12/2022 | 16/12/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
27/04/2023: The following changes were made to the trial record:
1. The target number of participants was changed from 180 to 198.
2. The recruitment end date was changed from 31/05/2023 to 21/04/2023.
3. The total final enrolment was added.
17/04/2023: The intention to publish date has been changed from 31/07/2023 to 31/07/2025.
12/04/2023: The recruitment end date has been changed from 30/04/2023 to 31/05/2023.
16/03/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 30/04/2023.
2. The overall end date was changed from 31/03/2023 to 31/07/2024.
3. The plain English summary was updated to reflect these changes.
16/12/2022: Publication reference added.
15/12/2022: A scientific contact was changed.
08/07/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/07/2022 to 31/12/2022.
2. The overall trial end date has been changed from 31/07/2022 to 31/03/2023 and the plain English summary updated accordingly.
3. The intention to publish date has been changed from 31/12/2022 to 31/07/2023.
30/03/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/08/2021 to 01/04/2022.
2. The recruitment end date has been changed from 31/12/2021 to 31/07/2022.
3. The overall trial end date has been changed from 31/12/2021 to 31/07/2022 and the plain English summary has been updated accordingly.
22/10/2021: Internal review.
15/06/2021: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/05/2021 to 01/08/2021.
2. The recruitment end date was changed from 30/06/2021 to 31/12/2021.
20/04/2021: The following changes were made to the trial record:
1. The publication and dissemination plan, was changed.
2. The participant level data, was changed from 'Other' to 'Available on request'
23/02/2021: The recruitment start date was changed from 15/02/2021 to 01/05/2021.
04/01/2021: Trial’s existence confirmed by National Institute for Health Research (NIHR).
