Plain English Summary
Background and study aims
Sepsis is a potentially life-threatening condition caused by a severe infection. When someone develops sepsis, inflammation occurs not just at the site of the infection but throughout the body. This widespread inflammation can be very harmful. Similar problems arise after cardiac arrest. Currently, the diagnosis of sepsis relies on time-consuming and insufficient microbial culture and assessment of blood proteins. There is a clear clinical need for a timely and accurate medical diagnosis. We will be looking in detail at proteins and genetic information that we suspect may help doctors to differentiate between patients with different type of infections and inflammation.
Who can participate?
We are recruiting a number of people with severe infections causing organ failure (also known as severe sepsis and septic shock) or who have suffered cardiac arrest.
What does the study involve?
In total, we will take 94 ml (about nine tablespoonfuls) of blood in addition to the blood tests that have been taken as part of normal care. We would also like to send a short questionnaire after 6 months to find out how the patients are doing. The questionnaire will take about 20 minutes to fill in.
What are the possible benefits and risks of participating?
There will be no benefit to the patients in taking part. It is unlikely that the extra blood samples could cause any harm because the volume of blood taken is small. The blood samples are taken out of one of the lines that are already in place as part of routine care there are no extra needles.
Where is the study run from?
Cardiff University (UK).
When is study starting and how long is it expected to run for?
The study started in March 2013 and will run until July 2014.
Who is funding the study?
The Technology Strategy Board (UK).
Who is the main contact?
Prof Judith E Hall OBE
hallje@cf.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Judith Hall
ORCID ID
Contact details
Institute of Infection and Immunity
Cardiff University
Heath Park Campus
Cardiff
CF14 4XN
United Kingdom
-
hallje@cf.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1.0
Study information
Scientific title
Analysis of geNe Expression and bioMarkers fOr poiNt-of-care dEcision support in Sepsis: a prospective observational study
Acronym
ANEMONES
Study hypothesis
This project will use two different approaches (a) genetic and (b) multiple protein assays to validate novel inflammatory or sepsis-associated markers identified by very complex statistics developed by Nottingham Trent University. This will enable us to differentiate between features specific to infection and those that are common to severe inflammation. The project will identify highly significant biological markers that will help us to rapidly diagnose sepsis early in the disease and differentiate it from severe inflammation.
Ethics approval
South Wales Research Ethics Committee Panel D; Ref: 12/WA/0303
Study design
Prospective observational study
Primary study design
Observational
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Sepsis, SIRS without infection
Intervention
We will study two patient groups: patients with severe sepsis from abdominal and pulmonary disease (n=160), and a positive control group. The positive control group will be patients with inflammation and organ failure not related to infection (n=40) and for this we will include patients admitted to the Intensive Care after out of hospital cardiac arrest.
The following blood samples will be taken from ICU patients with organ failure (all subjects):
5 ml heparinised blood frozen on days 1, 2, 5 and discharge for DNA micro-arrays and purification of PBLs
1 ml heparinised blood frozen on days 1, 2, 5 and discharge for storage
3 x heparinised 1.0 ml blood for platform development
2 ml EDTA blood on day 1 for CMV serology
2 ml EDTA blood on day 5 for CMV PCR
2 ml EDTA blood on day 1 for 16S PCR
7 ml clotted blood on day 1, day 2, day 5 and day of discharge for purification of serum and cytokine/protein biomarker analysis
6 ml EDTA blood on day 1, day 2, day 5 and day of discharge for purification of plasma and cytokine/protein biomarker analysis
The samples taken will undergo the following tests: 16S PCR, microarray analysis, qPCR analysis, proteomic analysis
Clinical data describing in detail the progress and severity of illness will be imported from the ICU clinical databases. Data items recorded will include physiological and routine laboratory variables. We will collect the following microbiology data:
Results of positive microbiology cultures including:
The date the sample was taken (days after admission)
The organism cultured
Results of 16S PCR if no positive cultures are isolated
2 ml samples for PCR will only be processed if no diagnostic cultures are recovered
Health questionnaire
We will conduct a survey amongst the survivors of the study who regained capacity, to assess their health-related quality of life using the SF-36 questionnaire. This short questionnaire will be sent to all survivors after 6 months of ICU discharge to be filled and returned by the participants.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
1. Document the biological (biomarker) profiles of patients with severe sepsis and septic shock using genomic and proteomic analysis from samples taken on day 1,2,5 and ICU discharge
2. Identify which combinations of biomarkers can give the best predictive information of how the patient will progress in their illness using genomic and proteomic analysis from samples taken on day 1, 2, 5 and ICU discharge
3. Assess quality of life after 6 months of ICU discharge in this cohort
Secondary outcome measures
Assess the utility of the biomarker panel in the clinical environment as point-of-care tests on suitable devices used near the bedside
Overall trial start date
01/03/2013
Overall trial end date
01/07/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged 16 years or over
2. Diagnosis of severe sepsis. Sepsis is defined as:
2.1. A defined focus of infection: indicated by either:
2.1.1. An organism grown in blood or sterile site OR
2.1.2. An abscess or infected tissue (e.g., pneumonia, peritonitis, urinary tract, vascular line infection, soft tissue, etc)
2.2. At least two systemic inflammatory response syndrome (SIRS) criteria. The four SIRS criteria are:
2.2.1. Core temperature >38°C or <36°C (core temperature is rectal, urinary bladder, central line, or tympanic). If oral, inguinal or axillary temperatures are used, add 0.5°C to the measured value. Hypothermia <36°C must be confirmed by core temperature only. Use the most deranged value recorded in the 24 hours before ICU admission.
2.2.2. Heart rate >90 beats/minute. If patient had an atrial arrhythmia, record the ventricular rate. If patients have a known medical condition or are receiving treatment that would prevent tachycardia (for example, heart block or beta blockers), they must meet two of the remaining three SIRS criteria. Use the most deranged value recorded in the 24 hours before ICU admission.
2.2.3. Respiratory rate > 20 breaths per minute or a PaCO2 < 4.3 kPa (32 mmHg) or mechanical ventilation for an acute process. Use the most deranged respiratory rate or PaCO2 recorded in the 24 hours before ICU admission.
2.2.4. White blood cell count of >12 x 109/l or < 4 x 109/l or > 10% immature neutrophils (band forms). Use the most deranged value recorded in the 24 hours before ICU admission.
3. Severe sepsis is defined as sepsis plus at least one organ failure, except when that organ failure was already present 48 hours before the onset of sepsis.
4. Organ failure is defined as a Sequential Organ Failure Assessment (SOFA) score > 2 for the organ in question
5. Presenting to hospital with abdominal or pulmonary sepsis of less than 72 hours duration
6. Patient already has or will require arterial cannulation as part of standard treatment
Inclusion criteria for critically ill patients without infection:
1. Patients admitted to the ICU following out-of hospital cardiac arrest
2. SIRS criteria as above
3. Organ failure criteria as above
4. Patients must not be receiving antibiotics for treatment of known or suspected infection
5. Patient already has or will require arterial cannulation as part of standard treatment
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
200
Participant exclusion criteria
1. Age less than 16 years
2. Pregnant
3. Severe immune deficiency, for example a diagnosis of AIDS
4. Anti-rejection transplant drugs
5. Methotrexate
6. High-dose corticosteriod treatment (>10 mg prednisolone/day or equivalent)
7. Severe liver failure
8. Childs III or worse
Recruitment start date
01/03/2013
Recruitment end date
01/07/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Institute of Infection and Immunity
Cardiff
CF14 4XN
United Kingdom
Funders
Funder type
Research organisation
Funder name
Technology Strategy Board (UK); Ref:101191
Alternative name(s)
TSB
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list