Validating Novel, Non-contrast Cardiac MRI Imaging in Haemodialysis Patients (CONFIRM)

Validating the Accuracy of Novel, Non-contrast, Cardiac Magnetic resOnaNce Imaging in Defining Myocardial FIbRosis in Patients With End-stage Renal Disease on haeModialysis: the CONFIRM Study

There are currently no good ways of measuring levels of scarring in the hearts of patients with advanced kidney disease and patients on dialysis, although recent research has shown a new cardiac MRI technique, called native T1 mapping, may provide a solution to this. To assess the accuracy of this novel technique in dialysis patients, it is essential to undertake a study which compares native T1 mapping to actual levels of scarring in the hearts of patients on dialysis.

Study Overview

• Status: Recruiting
• Conditions: End Stage Kidney Disease; Fibrosis Myocardial
• Intervention / Treatment: Diagnostic test: Cardiac MRI scan; Diagnostic test: Echocardiogram; Procedure: Cardiac explantation; Diagnostic test: 48-Hour continuous cardiac monitoring; Diagnostic test: Blood samples

Detailed Description

Native T1 mapping is a novel, non-contrast, cardiac MRI technique that characterises myocardial tissue by exploiting the different water content of tissues. It correlates well with histo-pathological levels of myocardial fibrosis in diseases of pressure overload such as aortic stenosis. There is growing evidence to demonstrate the potential of native T1 mapping as an imaging biomarker of myocardial fibrosis in patients with ESRD; myocardial native T1 values are higher in patients with ESRD than controls, and associate with measures of myocardial strain and circulating markers of cardiac dysfunction. Although native T1 times are affected by water content of tissues, our group has shown that native T1 times are not influenced by clinical changes in fluid status in HD patients and that the inter-study reproducibility and intra- and inter-observer variability of native T1 are outstanding.

Native T1 mapping is a promising, non-invasive imaging biomarker of myocardial fibrosis in patients with advanced renal disease. It is essential that the technique is validated against histology before further use in clinical studies.

The aim of this study is to directly assess the relationship between native T1 mapping and levels of MF examined at post-mortem in haemodialysis patients.

• Study Type: Observational
• Enrollment (Estimated): 9

Contacts and Locations

• Study Contact: Name: James Burton, DM, FRCP; Phone Number: +44 (0)116 2588043; Email: jb343@le.ac.uk
• Study Contact Backup: Name: Matthew Graham-Brown, MBChB, MRCP; Phone Number: +44 (0)116 2588043; Email: mgb23@le.ac.uk

Study Locations

• United Kingdom
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Recruiting
      • University Hospitals Of Leicester Nhs Trust
      • Contact: James Burton, FRCP; Phone Number: 01162588043; Email: jb343@le.ac.uk
      • Sub-Investigator: Matthew Graham-Brown, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The plans for patient recruitment were developed in partnership with our local haemodialysis patient participation and involvement group. Patients will be identified by means of a well established supportive care register for haemodialysis patients. These patients, and often their families, have engaged in discussion about end-of-life care, including discussions about limitations on care and preferred place of death.

Description

Inclusion Criteria:

• Prevalent haemodialysis patient (more than 3 months)
• Active on the supportive care register with anticipated death in the subsequent 12 months
• Able to give informed consent
• Consent to donation of heart for research following death
• Able to understand written and verbal explanations in English

Exclusion Criteria:

• Contraindication to MRI scan (e.g. pacemaker, incompatible metallic implants, claustrophobia)
• Patients with expected or potential infiltrative cardiomyopathy (e.g. amyloidosis)
• Unable to give informed consent
• Unable to understand written and verbal explanations in English

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Haemodialysis patients; The plans for patient recruitment were developed in partnership with our local haemodialysis patient participation and involvement group. Patients will be identified from the supportive care register established for haemodialysis patients in Leicester in 2008. Inclusion: Prevalent haemodialysis patient (more than 3 months); Active on the supportive care register with anticipated death in the subsequent 12 months; Able to give informed consent; Consent to donation of heart for research following death; Able to understand written and verbal explanations in English Exclusion: Contraindication to MRI scan (e.g. pacemaker, incompatible metallic implants, claustrophobia); Patients with expected or potential infiltrative cardiomyopathy (e.g. amyloidosis); Unable to give informed consent; Unable to understand written and verbal explanations in English

Diagnostic test: Cardiac MRI scan; A non-contrast cardiac MRI (CMR) scan at 3-Tesla platform (Skyra, Siemens Medical Imaging, Erlangen, Germany). This non-contrast CMR scan will principally determine: Left ventricular (LV) mass and volumes/ejection fraction and; fibrosis using T1 mapping.; Other Names: CMR; Diagnostic test: Echocardiogram; Assessments will include: LV size and function as per the American Society of Echocardiography guidelines. In addition specific focus will be paid end-diastolic integrated backscatter measurements.; Other Names: ECHO; Procedure: Cardiac explantation; A limited post-mortem will be performed to retrieve patients' hearts for preparation and storage at St George's University, London where direct comparison will be made between levels of scarring seen directly under the microscope between that on the MRI scans.; Diagnostic test: 48-Hour continuous cardiac monitoring; Attach continuous Holter monitor (Schiller, medilog®AR12 plus/AR4 plus/FD5 plus, Baar, Switzerland) that will start before dialysis and terminate just before the subsequent dialysis treatment 48h later.; Other Names: Holter; Diagnostic test: Blood samples; Collect blood samples from the arterial needle before dialysis. Approximately 30 millilitres of blood will be collected and then be pipetted into cryotubes and frozen at -80°C in an electronically monitored freezer for analysis in batches throughout the study. These samples will be used to investigate the relationship between circulating biomarkers of fibrosis, the MRI scans and the histological samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between MRI and histological measures of cardiac fibrosis	To assess the correlation between native T1 values measured using cardiac MRI in haemodialysis patients approaching the end of their lives, with histological samples analysed post-mortem.	Cardiac MRI performed within 12-months of histological samples obtained post-mortem

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of MRI versus ECHO in the measurement of cardiac fibrosis	Relationship between integrated backscatter (measured with echocardiography) and levels of myocardial fibrosis on histology measured at post-mortem.	Echocardiograms performed within 12-months of histological samples obtained post-mortem
Relationship between cardiac fibrosis and heart rhythm	Relationship between continuous Holter-monitor data and levels of myocardial fibrosis on histology measured at post-mortem.	Continuous Holter recording performed within 12-months of histological samples obtained post-mortem
Correlation between cardiac fibrosis and relevant circulating biomarkers	Relationship between humoral markers of cardiac dysfunction of fibrosis and levels of myocardial fibrosis on histology measured at post-mortem	Samples collected within 12-months of histological samples obtained post-mortem
Additional cardiac MRI techniques and the measurement of cardiac fibrosis	The relationship between additional, non-contrast CMR techniques and histology at post-mortem	Cardiac MRI performed within 12-months of histological samples obtained post-mortem

Collaborators and Investigators

• Sponsor: University of Leicester
• Collaborators: University Hospitals, Leicester; St George's, University of London
• Investigators: Principal Investigator: James Burton, DM, FRCP, Associate Professor in Renal Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 1, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Cardiac MRI; Hemodialysis; Myocardial Inflammation; Myocardial Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fibrosis; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 0674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The full study protocol will be published online, open access.
• IPD Sharing Time Frame: The protocol will be published within 12 months of registration.
• IPD Sharing Access Criteria: Open access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No