Evaluating a new test of the immune system to better understand recovery from a severe reaction to an infection (sepsis)
| ISRCTN | ISRCTN11364482 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11364482 |
| IRAS number | 286417 |
| Secondary identifying numbers | 20SM6207, IRAS 286417 |
- Submission date
- 23/09/2020
- Registration date
- 24/09/2020
- Last edited
- 01/05/2025
- 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 when severe infection leads to organ failure. It is a major global healthcare problem. Recent studies suggest as many as 49 million cases of sepsis worldwide each year leading to 11 million deaths. As sepsis care has improved more patients now recover from the early phases of sepsis but repeat occurrences are a major problem. Patients with sepsis often experience weakening of their immune systems known as immune suppression. This is now recognised as an important feature in a large proportion of patients who have sepsis and it leads to poor outcomes for these patients. At present there is no clinical test to assess the immune function of patients who have sepsis.
The IMPACCT study will investigate whether it is possible to use a new diagnostic test to identify and classify patients with sepsis who are at higher risk of poor outcomes and developing new infections. It is an observational study with no intervention or novel treatment introduced and no change to patients’ standard care and treatment when taking part.
Who can participate?
Participants will be adult patients in intensive care who are being, or have been, treated for suspected sepsis and are receiving, or have received, organ support. The patients will have been admitted to an ICU for over 48hours and less than 120 hours (5 days) and are expected to require ongoing care in an environment capable of providing organ support for at least one more calendar day.
What does the study involve?
The study research team will collect data on the patient’s medical condition throughout their treatment in hospital and will conduct a clinical diagnostic test on participants’ blood samples. Blood samples will be taken from patients at 3 time points during the study and will be taken from indwelling lines where present. The test is a rapid RNA-based diagnostic test that produces an Immune Profiling Panel (IPP). Test results will not be shared with the research team or influence patients’ care. Patients will be contacted 90 days after inclusion to complete a diary regarding their wellbeing and any new infections. Over a 2-year period, the study will recruit 600 patients in hospitals in the UK, France, and Sweden.
What are the possible benefits and risks of participating?
As an observational study with no treatment or intervention introduced to patients, there would not be a direct benefit to patients from this study but the results may help future patients and assist doctors in the future in treating people more effectively and successfully. There is no monetary benefit as participants will not be paid to participate.
The physical risks of taking part would be expected to be minimal. Taking blood samples can cause mild discomfort and bruising if taken from a vein. These procedures will only be carried out by an experienced health professional under sterile conditions to minimise these risks.
The study team have considered, and sought to mitigate, risks to patients’ data and samples. All data and samples will be collected, handled, processed and stored by the study team in a correct and respectful manner to the highest standards of confidentiality and security. The study will comply with all relevant UK and EU regulations regarding data protection and participants’ biological samples. Only de-identified or pseudonymised information would be shared between study partners.
In confirming capacity to consent and communicating with participants, study team members have extensive experience of assessing capacity and caring for patients in intensive care settings. The team is adept in providing information, answering questions from participants and their consultees, and considering the wishes and intentions of patients. The team will all have received training in IMPACCT processes and procedures and would work in accordance with the principles of Good Clinical Practice (GCP).
Where is the study run from?
The IMPACCT study is being organised and sponsored by Imperial College London in the UK and the Chief Investigator is Professor Anthony Gordon. Participants will be recruited from participating sites in the UK, France, and Sweden.
When is the study starting and how long is it expected to run for?
January 2020 to April 2024
Who is funding the study?
1. European Institute of Innovation & Technology (EIT) Health
2. bioMérieux (France)
3. National Institute for Health Research (UK)
Who is the main contact?
Mr Richard Cleaver, r.cleaver@imperial.ac.uk
Contact information
Public
Room 5.03
5th Floor, Medical School Building
Imperial College London
St Mary’s Campus
Norfolk Place
London
W2 1PG
United Kingdom
 ORCID ID |
0000-0001-5296-271X |
|---|---|
| Phone | +44 (0)7999 044627 |
| r.cleaver@imperial.ac.uk |
Scientific
Room 1091, QEQM building
St Mary's Hospital
Praed Sreet
London
W2 1PG
United Kingdom
| ORCID ID |
0000-0002-0419-547X |
|---|---|
| Phone | +44 (0)203 3126328 |
| anthony.gordon@imperial.ac.uk |
Study information
| Study design | Multi-centre prospective observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | IMPACCT: IMmune Profiling of ICU pAtients to address Chronic Critical illness and ensure healThy ageing |
| Study acronym | IMPACCT |
| Study objectives | There is a subgroup of patients who have sepsis, being treated in ICU, who have an immunosuppressed subphenotype that results in high HAI and mortality rates. Rapid identification of these patients using a clinical diagnostic test would allow more targeted treatment as part of a personalised medicine approach. |
| Ethics approval(s) | Approved 07/12/2020, London - South East Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH, UK; +44 (0)207 104 8085; londonsoutheast.rec@hra.nhs.uk), ref: 20/LO/1163 |
| Health condition(s) or problem(s) studied | Adult patients with suspected sepsis receiving organ support in an intensive care unit |
| Intervention | The IMPACCT study will investigate whether it is possible to identify and stratify patients with sepsis who are at higher risk of poor outcomes and developing new infections. It is an observational study with no intervention or novel treatment introduced and no change to patients’ standard care and treatment when taking part. Participants will be adult patients in intensive care who are being, or have been, treated for suspected sepsis. The study research team will collect data on the patient’s medical condition throughout their treatment in hospital and will conduct a clinical diagnostic test on participants’ blood samples. Blood samples will be taken from patients at 3 timepoints during the study and will be taken from indwelling lines where present. The test is a rapid RNA-based diagnostic test that produces an Immune Profiling Panel (IPP). Test results will not be shared with the research team or influence patients’ care. Patients will be contacted 90 days after inclusion to complete a diary regarding their wellbeing and any new infections. Over a 2-year period the study will recruit 600 patients in hospitals in the UK, France, and Sweden. |
| Intervention type | Other |
| Primary outcome measure | 90-day all-cause mortality and new hospital acquired infection rates up to 90 days or hospital discharge (whichever comes first) will be assessed through use of medical records and contacting participants to collect their responses. (New infections will be defined as: 1. Any new infection requiring treatment more than 48 hours after stopping treatment for a previous infection AND 2. Fulfilling a definition based on the criteria used in the REAnimation Low Immune Status Markers (REALISM) study (NCT02638779) and the European Centre for Disease Prevention and Control case definition for a hospital acquired infection from the suspected anatomical site, as determined by the senior treating clinician.) |
| Secondary outcome measures | Assessed through use of medical records and contacting participants to collect their responses: 1. 28-day all-cause mortality 2. ICU and hospital mortality rates 3. Duration of ICU stay, measured as ICU free days / number of days alive and outside of ICU, up to 28 days 4. Duration of organ support, measured as organ support free days / number of days alive without each organ support and also any organ support, up to 28 days in ICU. Organ support includes any of: extracorporeal gas exchange, invasive or non-invasive mechanical ventilation (including continuous positive pressure ventilation or non-invasive ventilation), high flow oxygen therapy (any flow ≥30L/min), vasopressor or inotrope support, any form of renal replacement therapy 5. Duration of Hospital stay, measured as hospital free days / number of days alive and outside of hospital, up to 90 days 6. Hospital readmission(s) as an inpatient up to day 90. We will also collect if any readmission was related to a new infection 7. Health-related quality of life at 90 days, measured using the EQ5D-5L questionnaire 8. New infections after hospital discharge up to day 90, collected via patient diaries |
| Overall study start date | 01/01/2020 |
| Completion date | 30/04/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 600 |
| Total final enrolment | 357 |
| Key inclusion criteria | 1. Age ≥18 years 2. Admitted to an ICU for ≥48 hours and <120 hours (5 days) 3. Being (or has been) treated for suspected sepsis during this ICU admission: 3.1. Intravenous antibiotics to treat a known / suspected infection 3.2. Acute organ dysfunction 4. Has received organ support (any of the following): 4.1. Respiratory – any form of mechanical ventilation, non-invasive ventilation or high-flow nasal oxygen for ≥24h, OR 4.2. Cardiovascular – any intravenous continuous infusion of vasopressor or inotrope for ≥24h, OR 4.3. Renal – any form of continuous renal replacement therapy for ≥24 or acute and new intermittent haemodialysis with at least two episodes 5. Is expected to require ongoing care in an environment capable of providing organ support (eg and ICU or HDU) for at least one more calendar day |
| Key exclusion criteria | 1. Severe neutropenia (neutrophil count <0.5 x 10(9)/L) due to an underlying disease / treatment (but not sepsis) 2. Corticosteroids (intravenously or oral) of more than an equivalent dose of prednisolone 0.1mg/kg for at least 7 days within the past 30 days (not as part of sepsis management) 3. Use of therapeutic antibodies during this admission 4. Onco-haematological disease (eg, lymphoma, leukaemia, myeloma) treated within the 5 years before inclusion 5. Allogenic hematopoietic stem cell transplantation (regardless of timing) 6. Chemotherapy or immunotherapy within the last 6 months prior to inclusion date 7. Innate immune deficiency (eg, severe combined immunodeficiency) 8. Acquired immune deficiency (eg HIV or AIDS, any stage) 9. Receiving any other immunosuppressive therapy (eg anti-TNF therapies) 10. Patients with a ‘withdrawal of life-sustaining treatment’ decision, at time of inclusion 11. Moribund and not expected to survive 24 hours 12. Participation in an interventional study of immunomodulating therapy or any other unlicensed therapy 13. Pregnant or breastfeeding women 14. No social security insurance (France only) 15. Patients with restricted liberty, prisoners or under legal protection 16. Previously enrolled in IMPACCT |
| Date of first enrolment | 29/03/2021 |
| Date of final enrolment | 30/11/2022 |
Locations
Countries of recruitment
- England
- France
- Sweden
- United Kingdom
Study participating centres
South Wharf Road
London
W2 1BL
United Kingdom
London
NW1 2PG
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
27 rue du Faubourg Saint-Jacques
Paris
75014
France
Huddinge
Stockholm
14186
Sweden
Sponsor information
University/education
Joint Research Compliance Office
Room 221, Level 2, Medical School Building
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +44 (0)20 7594 9480 |
|---|---|
| jrco.ctimp.team@imperial.ac.uk | |
| Website | https://www.imperial.ac.uk |
Funders
Funder type
Government
Government organisation / National government
No information available
No information available
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 | 31/12/2024 |
|---|---|
| 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 | Requests for access to the data from this study will be considered by the IMPACCT investigators, on submission of a request to the Chief Investigator, including a scientific rationale. The investigators will aim to share anonymous data from this study with important and valid scientific studies, subject to any ethics, regulatory and contractual requirements and subject to the signing of a data sharing agreement. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 03/03/2025 | 01/05/2025 | Yes | No |
Editorial Notes
01/05/2025: Publication reference and total final enrolment added.
18/07/2024: The overall end date was changed from 31/12/2023 to 30/04/2024.
17/04/2024: The following changes were made to the trial record:
1. The overall end date was changed from 26/04/2023 to 31/12/2023.
2. The intention to publish date was changed from 26/04/2024 to 31/12/2024.
3. The plain English summary was updated to reflect these changes.
09/11/2022: The recruitment start date was changed from 15/11/2020 to 29/03/2021.
08/11/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 15/11/2022 to 30/11/2022.
2. The overall end date was changed from 31/01/2023 to 26/04/2023.
3. The intention to publish date was changed from 30/11/2023 to 26/04/2024.
4. The plain English summary was updated to reflect these changes.
5. The ethics approval was added.
6. The participant level data sharing statement was added.
20/11/2020: The following changes were made to the trial record:
1. The recruitment start date
2. The ethics committee details were added.
3. The trial website was added.
20/10/2020: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/10/2020 to 15/11/2020.
2. The recruitment end date was changed from 31/10/2020 to 15/11/2022.
3. The overall trial end date was changed from 31/10/2022 to 31/01/2023.
4. The intention to publish date was changed from 31/10/2023 to 30/11/2023.
24/09/2020: Trial’s existence confirmed by Imperial College Healthcare NHS Trust.
