Validation of Quantitative Myocardial Tissue Characterization Through Non-gated CT
Primary Purpose
Cardiac Disease, Covid19, Cardiotoxicity
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Cardiac Magnetic Resonance
Additional CT acquisition
Blood tests
Sponsored by
About this trial
This is an interventional diagnostic trial for Cardiac Disease focused on measuring Tomography X-Ray Computed, Magnetic Resonance Imaging, Cardiotoxicity, Extracellular Space
Eligibility Criteria
Inclusion Criteria:
- Patients referred for contrast-enhanced cardiac CT
- Age 18 to 80 years
Exclusion Criteria:
- Absolute contraindications to CMR
- Implantable cardioverter defibrillators and ferromagnetic thoracic devices which may cause artifacts at magnetic resonance imaging
- Previous allergic reactions to gadolinium-based contrast agents
- Pregnancy
- Severe obesity
- Severe claustrophobia
- Too low image quality to perform post-processing analyses
Sites / Locations
- IRCCS Policlinico San DonatoRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
Outcomes
Primary Outcome Measures
Validation of CT-MRE as a surrogate of CMR-ECV
CT-MRE will be calculated as (1-hematocrit) multiplied by the ratio of the differences in image density between post- and pre-contrast images in the myocardium and blood pool. Thus, CT-MRE will be represented by a percentage value. It will be calculated by placing regions of interest on the appropriate CT images.
Secondary Outcome Measures
Assessment of correlations between CMR-derived myocardial strain, CMR-ECV and CT-MRE
Myocardial strain will be calculated via feature tracking algorithms, segmenting the endocardium and epicardium on cine images. As strain represents the ratio between the difference in displacement of the myocardial wall and its original position, it will be represented by a percentage. Strain will be measured in its longitudinal, radial and circumferential components.
Role of ECV as a biomarker of chronic cardiac damage following SARS-CoV-2 infection
ECV will be calculated as the product between (1-hematocrit) and the ratio of the differences in image intensity between pre- and post-contrast T1 maps in the myocardium and blood pool. Data for this calculation will be derived by placing regions of interest in the appropriate MRI T1 maps. ECV is thus represented by a percentual value
Full Information
NCT ID
NCT04880317
First Posted
May 2, 2021
Last Updated
September 12, 2022
Sponsor
IRCCS Policlinico S. Donato
Collaborators
Ospedale San Raffaele
1. Study Identification
Unique Protocol Identification Number
NCT04880317
Brief Title
Validation of Quantitative Myocardial Tissue Characterization Through Non-gated CT
Official Title
Validation of Quantitative Myocardial Tissue Characterization Through Contrast-enhanced Non-gated CT Versus CMR: The VALETUDO-CT Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 7, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS Policlinico S. Donato
Collaborators
Ospedale San Raffaele
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The main aim is to validate non-gated 5-min computed tomography myocardial relative enhancement (CT-MRE), which can be readily estimated via contrast-enhanced non-gated chest CT, as a tool for estimating myocardial extracellular volume (ECV) using cardiac magnetic resonance (CMR)-derived ECV as a reference standard in a consecutive series of patients scheduled for cardiac CT.
A secondary explorative aim is to evaluate the presence and extent of possible myocardial alterations in those patients enrolled in the VALETUDO study who have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Detailed Description
Patients scheduled to undergo contrast-enhanced cardiac CT and meeting inclusion criteria will be proposed enrolment in the study, and as such they will be informed on the study aims and design and will be invited to sign a specific informed consent. All potential enrollees will be invited to undergo an additional CT acquisition as part of their cardiac CT examination, to estimate CT-MRE, blood tests, and a contrast-enhanced CMR scan. All those meeting exclusion criteria (contraindications to CMR, previous allergic reactions to gadolinium-based contrast agents, pregnancy, severe obesity, claustrophobia) will be consequently excluded from the study. Patients with a previous diagnosis of COVID-19 will not be excluded if they are declared negative according to the procedure provided for by the regulations in force.
For all those eventually included to participate in the study, the CT examination will include the addition of a non-gated 5-min delayed acquisition, allowing the assessment of CT-MRE. All enrolled patients will then undergo blood tests including the assessment of haematocrit for the calculation of ECV and CT-MRE, and serological testing for COVID-19 antibodies. An additional blood sample (for a total of 30 ml of venous blood) will be tested for myocardial fibrosis biomarkers (Troponin, Osteopontin, ST, and Osteocalcin), and the remaining samples will be long-term bio-banked pending patients' approval.
All enrolled patients will then undergo a CMR examination within 10 days of the cardiac CT scan, including the intravenous administration of a macrocyclic gadolinium-based contrast agent, including cine sequences for myocardial function and strain assessment, and native- and contrast-enhanced T1 mapping for myocardial ECV calculation.
Myocardial CT-MRE and CMR-derived ECV calculation will be conducted according to methods previously described by the two centres. All CT and CMR exams will be anonymized, and segmentation for such purposes will be performed by readers with extensive experience in cardiovascular CT and CMR. Additionally, myocardial strain will be calculated from CMR cine sequences, through dedicated software.
Taking into consideration the known correlation between CT- and CMR-derived ECV and given the correlation between CT-MRE and CT-derived ECV noted in a previous study from our group, we would expect the coefficient of the correlation between CT-MRE and CMR-derived ECV not to be lower than 0.3. On these grounds, aiming for an α error of 0.05 and a statistical power (1 - β) of 0.90, we would require a sample size of 113 patients for our principal aim. Considering a potential maximum dropout rate around 40% (mostly due to the refusal to undergo CMR on a subsequent date from cardiac CT), we aim to enrol 188 patients for our study.
Normality will be evaluated using Shapiro-Wilk test. In case of normal distribution, t-tests will be used to assess differences between groups, and Pearson's r will be used for correlations. In case of non-normal distributions, Mann-Whitney and Wilcoxon tests will be used to assess differences, and Spearman's ρ for correlations. P-values ≤0.05 will be considered as indicative of statistical significance.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Disease, Covid19, Cardiotoxicity, Extracellular Space Alteration
Keywords
Tomography X-Ray Computed, Magnetic Resonance Imaging, Cardiotoxicity, Extracellular Space
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
188 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Intervention Type
Diagnostic Test
Intervention Name(s)
Cardiac Magnetic Resonance
Intervention Description
All enrolled patients will undergo a contrast-enhanced CMR examination for the assessment of extracellular volume
Intervention Type
Diagnostic Test
Intervention Name(s)
Additional CT acquisition
Intervention Description
All enrolled patients will undergo an additional CT scan at 5 minutes post-contrast injection to evaluate myocardial relative enhancement
Intervention Type
Diagnostic Test
Intervention Name(s)
Blood tests
Intervention Description
Patients will undergo blood tests to review hematocrit, Sars-CoV-2 antibody status and cardiac fibrosis biomarkers
Primary Outcome Measure Information:
Title
Validation of CT-MRE as a surrogate of CMR-ECV
Description
CT-MRE will be calculated as (1-hematocrit) multiplied by the ratio of the differences in image density between post- and pre-contrast images in the myocardium and blood pool. Thus, CT-MRE will be represented by a percentage value. It will be calculated by placing regions of interest on the appropriate CT images.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Assessment of correlations between CMR-derived myocardial strain, CMR-ECV and CT-MRE
Description
Myocardial strain will be calculated via feature tracking algorithms, segmenting the endocardium and epicardium on cine images. As strain represents the ratio between the difference in displacement of the myocardial wall and its original position, it will be represented by a percentage. Strain will be measured in its longitudinal, radial and circumferential components.
Time Frame
3 months
Title
Role of ECV as a biomarker of chronic cardiac damage following SARS-CoV-2 infection
Description
ECV will be calculated as the product between (1-hematocrit) and the ratio of the differences in image intensity between pre- and post-contrast T1 maps in the myocardium and blood pool. Data for this calculation will be derived by placing regions of interest in the appropriate MRI T1 maps. ECV is thus represented by a percentual value
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patients referred for contrast-enhanced cardiac CT
Age 18 to 80 years
Exclusion Criteria:
Absolute contraindications to CMR
Implantable cardioverter defibrillators and ferromagnetic thoracic devices which may cause artifacts at magnetic resonance imaging
Previous allergic reactions to gadolinium-based contrast agents
Pregnancy
Severe obesity
Severe claustrophobia
Too low image quality to perform post-processing analyses
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francesco Sardanelli, MD
Phone
0252774468
Email
francesco.sardanelli@unimi.it
Facility Information:
Facility Name
IRCCS Policlinico San Donato
City
San Donato Milanese
State/Province
Milano
ZIP/Postal Code
20097
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Sardanelli
First Name & Middle Initial & Last Name & Degree
Francesco Sardanelli, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Validation of Quantitative Myocardial Tissue Characterization Through Non-gated CT
We'll reach out to this number within 24 hrs