CharacterisatiON of carDiac funCTion in Intensive Care Unit Survivors of Sepsis.

Heart Failure Clinical Trial

— CONDUCT-ICU  

Official title:

CharacterisatiON of carDiac funCTion in Intensive Care Unit Survivors of Sepsis (CONDUCT-ICU): A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05633290
• Other study ID #: GN22CA029
• Status: Recruiting
• Start date: March 1, 2023
• Est. completion date: February 2024

Study information

• Verified date: March 2023
• Source: NHS Greater Glasgow and Clyde
• Contact: Philip McCall, MBChB, MD
• Phone: 0141 951 5000
• Email: philip.mccall[@]glasgow.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Participants 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 provided them with an information sheet and written consent form. Participants 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. Participants 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. Participants 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

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. 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 researchers 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 researchers will invite them to the research facility within the local 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 69
• Est. completion date: February 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of informed consent.

2. Age > 18 years.

3. ICU admission with sepsis (According to The Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3])17

4. Ability to comply with study procedures

Exclusion Criteria:

1. Inability to give informed consent

2. Pregnancy.

3. Ongoing participation in any investigational research that may undermine the scientific basis of the study.

4. Contraindications to magnetic resonance imaging:

i. 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 v. Severe claustrophobia

5. Known Coronary Artery Disease

6. Previous Myocardial Infarction

7. Chronic Heart Failure prior to ICU admission

8. Patient receiving immune modulating drug or biologic therapy either long term or during acute admission

9. Patient considered by the clinical team to be very unlikely to survive to hospital discharge

10. Hospital Admission because of Covid-19

11. Patients undergoing treatment for malignancy with systemic anti-cancer therapies.

Related Conditions & MeSH terms

• Heart Failure
• Myocarditis
• Sepsis
• Septic Shock
• Toxemia

Intervention

Diagnostic Test:
• CMR
CMR Imaging 6-10 weeks post hospital discharge.
• hs-troponin
Biomarker of myocardial injury
• NT-pro BNP
Biomarker for heart failure
• CRP
Acute phase inflammatory marker
• IL1-B
Inflammatory biomarker
• IL-6
Inflammatory Biomarker
• IL-10
Inflammatory Biomarker
• TNF-alpha
Inflammatory Biomarker

Locations

Country	Name	City	State
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	University Hospital Crosshouse	Kilmarnock

Sponsors (4)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	Golden Jubilee National Hospital, NHS Ayrshire and Arran, University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left Ventricular Ejection Fraction	LVEF is a validated marker of cardiovascular function. It can be used in diagnosis of heart failure and can assist in grading severity.	6-10 weeks post hospital discharge
Secondary	hs-Troponin (ng/L)	Marker of myocardial injury commonly used in clinical practice	6-10 weeks post-hospital discharge
Secondary	NT-proBNP (pg/ML)	Biomarker of myocardial dysfunction used in patients with heart failure and associated conditions.	6-10 weeks post-hospital discharge
Secondary	CRP (mg/L)	Acute phase biomarker of inflammation.	6-10 weeks post discharge
Secondary	IL-10 (pg/ml)	Inflammatory cytokine thought to inhibit innate immune response.	6-10 weeks post discharge
Secondary	IL-1B (pg/ml)	Acute phase inflammatory cytokine and pyrogen.	6-10 weeks post discharge
Secondary	TNF-alpha (pg/ml)	Inflammatory cytokine implicated in acute inflammation and targeted for management of inflammatory and autoimmune disease	6-10 weeks post discharge
Secondary	IL-6 (pg/ml)	Inflammatory biomarker associated with adverse cardiovascular outcomes and adverse mortality in critically ill patients	6-10 weeks post discharge
Secondary	Brief Pain Inventory Score	Validated Assessment of Pain. Scores of 0 indicate no pain and scores of 10 indicate the 'worst pain you can imagine'.	6-10 weeks post discharge
Secondary	ID Pain Score	Validated assessment tool for differentiation of neuropathic pain. Patients describe character of pain using 'yes' or 'no' questions.	6-10 weeks post discharge
Secondary	EuroQol 5-Dimension (5D) Score	Validated measure of quality of life. Part of core outcome measures in critical illness survivors. Scores 5 domains (Mobility, Self-Care, Usual Activities, Pain/Discomfort, Anxiety /Depression) on likert scale as follows: 1) No problems, 2) Slight Problems, 3) Moderate Problems, 4) Severe Problems, 5) Unable	6-10 weeks post discharge
Secondary	Hospital Anxiety and Depression Score	Validated measure of anxiety and depression. Previously used in survivors of critical illness. Total score: 0-7 = Normal, 8-10 Borderline abnormal (borderline case), 11-21 Abnormal (case)	6-10 weeks post discharge
Secondary	Dukes Activity Status Index	Validated tool for assessing functional capacity. Scores 0 - 58.2, with higher scores indicating better functional capacity.	6-10 weeks post discharge
Secondary	Vitality Domain of Short Form 36 - Score	Validated tool for vitality and used in survivors of critical illness. Likert Scale Assessing vitality. Answers range from 1)All of the time, most of the time, a good bit of the time, some of the time, a little bit of the time, none of the time.	6-10 weeks post discharge
Secondary	MRC Breathlessness Scale	Widely used grading system for breathlessness in survivors of critical illness. Graded 0-4.4 indicates more severe breathlessness.	6-10 weeks post discharge
Secondary	Myocardial Native T1 and T2 Mapping	CMR markers of subtle inflammation and fibrosis commonly examined during CMR imaging.	6-10 weeks post discharge
Secondary	Successful follow-up rate of participants invited to attend CMR scans. i.e. Feasibility of CMR imaging	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.	6-10 weeks post discharge