CONDUCT-ICU: CharacterisatiON of carDiac funCTion in Intensive Care Unit Survivors of Sepsis.
Study Details
Study Description
Brief Summary
Cardiac dysfunction is common following hospital admission with sepsis and one of the most frequent causes for readmissions to hospital, however underlying mechanisms by which this might occur are unclear. The CONDUCT-ICU investigators will conduct a pilot, cohort study, characterizing cardiac function in ICU survivors of sepsis using a combination of CMR imaging, biomarkers and patient reported outcome measures to investigate mechanisms of cardiac dysfunction following sepsis. Comparisons will be made to that of the general population.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Sepsis is one of the most common reasons for admission to ICU in the UK and it is well established that adverse cardiovascular events are common following sepsis. In fact, the risk of adverse cardiovascular events such as MI, Heart Failure and Stroke is in excess of 60% greater compared to those who have not had sepsis. Similarly, heart failure is one of the most common causes of readmission to hospital following an episode of sepsis. The underlying mechanisms for this phenomenon are unclear and CONDUCT-ICU investigators intend on answering this question.
Investigators will collect cardiac and inflammatory biomarkers from participants at the point of discharge from ICU. Following discharge from hospital, cardiac magnetic resonance (CMR) scans of the heart will be undertaken in participants 6-10 weeks post-discharge from hospital to examine for evidence of inflammation in the heart. Further blood samples will also be collected to look for evidence of inflammation and heart muscle injury at this point in addition to patient reported outcomes measures using validated questionnaires.
Patients will be identified with their direct clinical team in ICU and are nearing or at the point of discharge from ICU. If eligible for the study, they will be approached by researchers and we will provide them with the information sheet and written consent form. They will be given up to 24hrs to decide if they wish to take part in research and if so, they will sign the consent form. They are free to withdraw from the study at any time, without any reason given, and this would not affect the standard of care they receive.
This is an observational cohort study. If willing to take part, participants will receive the normal follow-up that would be undertaken following discharge from ICU. In addition, researchers will collect a sample of blood from participants at the time of discharge from ICU and again at 6 -10 weeks post discharge. A Cardiac Magnetic Resonance (CMR) scan will be undertaken 6-10 weeks follow up.
Researchers will assess the patient's day-to-day function and quality of life by asking them to complete validated questionnaires. These questionnaires should take five to ten minutes to complete and help will be available if required. They will complete these questionnaires at the follow-up visit 6-10 weeks following discharge from hospital with the help of the researchers conducting the study
Cardiac magnetic resonance imaging (MRI) uses a powerful magnetic field, radio waves and a computer to produce detailed pictures of the structures within the heart. It is used to detect or monitor cardiac disease and to evaluate the heart's structure and function. Cardiac MRI does not use ionizing radiation, unlike x-rays, and it may provide images of the heart that are better than other imaging methods for certain conditions. MRI scanning takes around 30-40 mins and can be noisy therefore patients will be allowed to wear headphones/earplugs to block out the sound. Some people find the MRI scanner claustrophobic and it may therefore not be appropriate for them to take part in the study.
When undertaking CMR scans we will need to administer contrast to undertake complete studies for analysis. The contrast will be administered via a cannula, a small plastic tube that we commonly use to give medications and will almost certainly have been used during the patients ICU stay. Where possible we will aim to take the blood samples at the point of insertion of the cannula and so no extra needles will be involved.
The first blood sample will be collected following discharge from ICU whilst the patient is still in hospital. Further blood samples will be collected 6-10 weeks following discharge from hospital. We will take 16mls of blood each time. Blood samples for patients undergoing CMR will be taken when they attend for scan. Blood sampling for patients who do not undergo CMR imaging will attend for a separate follow-up visit for collection of samples.
Patients are normally invited to attend ICU follow-up via the InS:PIRE service at approximately 6-10 weeks post-discharge. Where possible we will combine blood sample analysis with routine follow-up visits in clinic to which participants would normally be invited. If they are not able to attend follow-up and are not attending for CMR scan, then we will invite them to our research facility within the research sites for collection of samples.
Samples will be stored in NHS Biorepository and analyzed within the British Heart Foundation Laboratory at the University of Glasgow.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| ICU Survivors of Sepsis ICU survivors of sepsis who would routinely attend ICU follow-up. |
Diagnostic Test: CMR
CMR Imaging 6-10 weeks post hospital discharge.
Diagnostic Test: hs-troponin
Biomarker of myocardial injury
Diagnostic Test: NT-pro BNP
Biomarker for heart failure
Diagnostic Test: CRP
Acute phase inflammatory marker
Diagnostic Test: IL1-B
Inflammatory biomarker
Diagnostic Test: IL-6
Inflammatory Biomarker
Diagnostic Test: IL-10
Inflammatory Biomarker
Diagnostic Test: TNF-alpha
Inflammatory Biomarker
|
Outcome Measures
Primary Outcome Measures
- Left Ventricular Ejection Fraction [6-10 weeks post hospital discharge]
LVEF is a validated marker of cardiovascular function. It can be used in diagnosis of heart failure and can assist in grading severity.
Secondary Outcome Measures
- hs-Troponin (ng/L) [6-10 weeks post-hospital discharge]
Marker of myocardial injury commonly used in clinical practice
- NT-proBNP (pg/ML) [6-10 weeks post-hospital discharge]
Biomarker of myocardial dysfunction used in patients with heart failure and associated conditions.
- CRP (mg/L) [6-10 weeks post discharge]
Acute phase biomarker of inflammation.
- IL-10 (pg/ml) [6-10 weeks post discharge]
Inflammatory cytokine thought to inhibit innate immune response.
- IL-1B (pg/ml) [6-10 weeks post discharge]
Acute phase inflammatory cytokine and pyrogen.
- TNF-alpha (pg/ml) [6-10 weeks post discharge]
Inflammatory cytokine implicated in acute inflammation and targeted for management of inflammatory and autoimmune disease
- IL-6 (pg/ml) [6-10 weeks post discharge]
Inflammatory biomarker associated with adverse cardiovascular outcomes and adverse mortality in critically ill patients
- Brief Pain Inventory Score [6-10 weeks post discharge]
Validated Assessment of Pain
- ID Pain Score [6-10 weeks post discharge]
Validated assessment tool for differentiation of neuropathic pain
- EuroQol 5D Score [6-10 weeks post discharge]
Validated measure of quality of life. Part of core outcome measures in critical illness survivors.
- Hospital Anxiety and Depression Score [6-10 weeks post discharge]
Validated measure of anxiety and depression. Previously used in survivors of critical illness.
- Dukes Activity Status Index [6-10 weeks post discharge]
Validated tool for assessing functional capacity.
- Vitality Domain of Short Form 36 - Score [6-10 weeks post discharge]
Validated tool for vitality and used in survivors of critical illness.
- MRC Breathlessness Scale [6-10 weeks post discharge]
Widely used grading system for breathlessness in survivors of critical illness. Graded 0-4.
- Myocardial Native T1 and T2 Mapping [6-10 weeks post discharge]
CMR markers of subtle inflammation and fibrosis commonly examined during CMR imaging.
- Successful follow-up rate of participants invited to attend CMR scans. i.e. Feasibility of CMR imaging [6-10 weeks post discharge]
To evaluate feasibility of undertaking CMR in complex post-ICU cohort of patients. To the investigators' best knowledge, this cohort has never been investigated before in this way and it is unclear to what extent participants will be able to attend follow up. We will evaluate the attendance rate at CMR follow-up measured against participants invited to take part in the study.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of informed consent.
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Age > 18 years.
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ICU admission with sepsis (According to The Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3])17
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Ability to comply with study procedures
Exclusion Criteria:
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Inability to give informed consent
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Pregnancy.
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Ongoing participation in any investigational research that may undermine the scientific basis of the study.
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Contraindications to magnetic resonance imaging:
- Cardiac pacemaker, artificial heart valve, neurostimulator, cochlear implant ii. Aneurysm clips iii. Metal injuries to the eye iv. Loose metal in any part of the body
- Severe claustrophobia
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Known Coronary Artery Disease
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Previous Myocardial Infarction
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Chronic Heart Failure prior to ICU admission
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Patient receiving immune modulating drug or biologic therapy either long term or during acute admission
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Patient considered by the clinical team to be very unlikely to survive to hospital discharge
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Hospital Admission because of Covid-19
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Patients undergoing treatment for malignancy with systemic anti-cancer therapies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Glasgow Royal Infirmary | Glasgow | United Kingdom | G4 0SF | |
| 2 | University Hospital Crosshouse | Kilmarnock | United Kingdom | KA2 0BE |
Sponsors and Collaborators
- NHS Greater Glasgow and Clyde
- NHS Ayrshire and Arran
- Golden Jubilee National Hospital
- University of Glasgow
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GN22CA029