Personalization of CM Injection Protocols in Coronary Computed Tomographic Angiography (PeopleCT)

March 19, 2019 updated by: Joachim Wildberger, Maastricht University Medical Center

Cardiac computed tomography (CCT) is one of the standard non-invasive imaging techniques allowing imaging of the heart and coronary arteries with a high temporal and spatial resolution. The high sensitivity and negative predictive value (NPV) of coronary CT angiography (CCTA) make it a valuable tool in the assessment of coronary artery disease (CAD) in patients with low to intermediate risk for CAD, especially to rule out CAD. This risk stratification can be done with help of multiple different risk-calculators (e.g. the updated Diamond-Forrester model by Genders et al. 2012). These calculators take different variables into account, e.g. advanced age, gender, blood pressure, diabetes mellitus (DM), lipid profile and smoking.

The aim of CCTA is a high diagnostic accuracy, which depends on both optimal intravascular enhancement (in Hounsfield Units; minimal 325 HU) and contrast-to-noise ratio (CNR). Optimal intravascular enhancement and CNR depend on different factors such as scan technique (e.g. tube voltage, tube potential), parameters of the administered contrast material (CM) and patient related factors (e.g. cardiac output (CO), body weight (BW)).

Patients with cardiac diseases often have multiple risk factors for developing contrast induced nephropathy (CIN), e.g. diabetes mellitus, advanced age, hypertension and chronic kidney disease. Although the relationship between CTA and CIN has recently come to discussion (AMACING trial; Nijssen et al. 2017), it is still desirable to minimise the CM volume used in these patients. One method to reduce the CM volume is to personalise the injection protocols. The personalisation of injection protocols to the individual patient is gaining more attention in the field of CT imaging. The goal is to individualise the injection protocols to a level, where the patient only receives the minimal amount of CM needed to acquire a diagnostic scan, while maintaining a diagnostic image quality. Many techniques are available and have been studied, e.g. adjustment of CM volume to scan protocol, CO, lean body weight (LBW) and BW.

However, no data is available on which of these is the most beneficial method for the personalisation of CM injection protocols. Therefore, the aim of this study is to assess the performance of three different personalized injection protocols (based on CO, LBW and BW) in CCTA with regard to image quality in comparison to previously used protocols in our department. We hypothesize that the personalized injection protocols will be non-inferior, provide a homogenous coronary enhancement (less non-diagnostic scans) in patients, and will account for a reduction of CM volume in our department in comparison to the previously used protocols.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cardiac diseases still are the leading cause of death in the western world. Besides the high mortality of the cardiac disease itself, recent studies have shown an increasing evidence of the prognostic value of cardiac diseases, particularly coronary artery disease (CAD), in a broad variety of other diseases. Especially in patients with oncological pathologies undergoing radiotherapy or lung resection surgery [Ambrogi et al. 2003; Kanzaki et al. 2017; Khakoo et al. 2008; Basacaraju et al. 2002; Fajardo et al. 1972]. Cardiac computed tomography angiography (CCTA) is one of the standard non-invasive imaging techniques allowing imaging of the heart and coronary arteries with a high temporal and spatial resolution. The high sensitivity and negative predictive value (NPV) of CCTA make it a valuable tool in the assessment of CAD. Especially to rule out CAD in patients with low to intermediate risk for CAD [Hendel et al. 2006; Goldstein et al. 2011; Budoff et al. 2008; Meijboom et al. 2008; Roffi et al. 2016].

The aim of CCTA is to achieve a high diagnostic accuracy, which depends on both optimal intravascular enhancement (in Hounsfield Units (HU); minimal 325 HU) and contrast-to-noise ratio (CNR). Optimal intravascular enhancement and CNR depend on multiple factors, such as scan technique (e.g. tube voltage (kV) and tube potential), parameters of the administered contrast material (CM) (e.g. concentration, flow rate) and patient related factors (e.g. body weight (BW), heart rate or cardiac output [CO]) [Bae et al. 2004; Awai et al. 2004]. Dedicated CT protocols are necessary to image the heart and the coronary arteries. These protocols require a correlation to the patient's electrocardiogram (ECG) in order to minimize cardiac motion and deliver a sharp image of the heart and coronary arteries. Depending on the heart rate of the patient, the scan can either be a prospectively ECG-triggered high-pitch or adaptive sequence, or retrospectively ECG-gated helical scan.

Patients with cardiac diseases often have multiple risk factors for developing contrast induced nephropathy (CIN), e.g. diabetes mellitus (DM), advanced age, hypertension, cardiovascular disease and chronic kidney disease. Although the relationship between CTA and CIN has recently come to discussion (AMACING trial; Nijssen et al. 2017), it is still desirable to minimise the CM volume used in these patients. Multiple strategies have been studied to reduce CM volume in CTA imaging [Kok et al 2016; Kok et al. 2015; Kok et al. 2016; Kok et al. 2016, Mihl et al. 2016; Seehofnerova et al. 2015; Hendriks et al. 2016]. For instance, lowering tube voltage to achieve a higher attenuation, the latter explained by the fact that mean photon energy of lower tube voltage settings in the x-ray beam moves closer to the K-edge of iodine (33.2 keV).

The personalisation of injection protocols to the individual patient is gaining more attention in CT imaging, and the goal is to individualise the injection protocols to a level, where the patient only receives the minimal amount of CM needed to make a diagnostic scan with a diagnostic image quality. Besides the techniques mentioned above, other techniques are possible, e.g. adjustment according to patients CO, lean body weight (LBW), and BW.

Both blood volume and CO increase with an increasing BW. When CO increases, the distribution of CM is also increased. On one hand this results in a fastened test bolus arrival, on the other hand in a decreased and shortened intravascular attenuation profile (in comparison to a decreased CO) [Bae KT 2010]. Therefore, both timing and CM volume can be adjusted to CO in order to achieve a similar intravascular attenuation profile.

LBW is a measurement for body fat percentage. It is known that fatty tissue is not as well vascularised in comparison to muscle tissue. Thus with increasing BW due to fatty tissue, the blood volume does not increase linear to BW. For instance, patients with a high BW due to increased muscle tissue, need more CM volume compared to patients with a high BW due to fatty tissue. The concept of LBW accounts for this fact [Bae KT 2010].

When adjusting CM volume to BW, less CM volume is needed with a lower BW in comparison to a higher BW, due to the decreased blood volume and CO [Bae KT 2010].

The tube voltage, set by automated tube voltage selection (ATVS, CAREkV, Siemens, Berlin, Germany), needs to be taken into account as well. CAREkV is a software program which chooses the optimal tube voltage (kV) and tube current (mAs) settings for the individual patient, based on their topograms, while maintaining a diagnostic image quality. Lower kV settings result in a higher intravascular enhancement if the same amount of CM is used, thus giving the potential to decrease CM volume in lower kV settings.

Since no data exist on the optimal method of choice, the aim of this study is to assess the performance of three personalized injection protocols (CO, LBW and BW) in CCTA, in comparison to previously used protocols, with regard to image quality. Secondly we want to assess the presence and severity of CAD in patients undergoing CCTA with help of the coronary artery disease reporting and data system (CAD-RADS).

A total of 330 patients will be included in this prospectively observer blinded randomized controlled non-inferiority trial. All patients will be randomised in one of three groups (CO, LBW and BW) with help of a randomisation software program (ALEA). The control group will consist of 110 consecutive patients who will be included retrospectively.

Study Type

Interventional

Enrollment (Actual)

327

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Zuid-Limburg
      • Maastricht, Zuid-Limburg, Netherlands, 6202AZ
        • Maastricht University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients referred for CCTA;
  • Age > 18 years;
  • Informed consent obtained.

Exclusion Criteria:

  • Inability to perform a breath hold for the expected scan time;
  • Hemodynamic instability;
  • Pregnancy;
  • Renal insufficiency (defined as glomerular filtration rate (GFR) < 30 mL/min);
  • Iodine allergy;
  • Age < 18 years;
  • Absence of informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Body Weight (BW)
Patients referred for CCTA in this group receive a personalised contrast media protocol. Contrast media administration based on body weight.
Other: Contrast media administration
All patients will receive contrast media with a concentration of 300 mg I/mL (Iopromide 300). The flowrate and volume will be calculated with help of the different formulas belonging to the three different arms.
ACTIVE_COMPARATOR: Cardiac output (CO)
Patients referred for CCTA in this group receive a personalised contrast media protocol. Contrast media administration based on cardiac output.
Other: Contrast media administration
All patients will receive contrast media with a concentration of 300 mg I/mL (Iopromide 300). The flowrate and volume will be calculated with help of the different formulas belonging to the three different arms.
ACTIVE_COMPARATOR: Lean Body weight (LBW)
Patients referred for CCTA in this group receive a personalised contrast media protocol. Contrast media administration based on Lean Body Weight.
Other: Contrast media administration
All patients will receive contrast media with a concentration of 300 mg I/mL (Iopromide 300). The flowrate and volume will be calculated with help of the different formulas belonging to the three different arms.
NO_INTERVENTION: Control group
Patients in this group will be included retrospectively and have received the standard CM injection protocol previously used in our department.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Image quality
Time Frame: 1 year
To evaluate the performance of the individualised injection protocols in CCTA, with regard to intravascular attenuation (minimal 325 HU) and compare them with the control group (non-inferiority).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective image quality
Time Frame: 1 year
The performance of the individualised injection protocols in CCTA with regard to objective image quality (image noise, CNR and SNR as calculated from the intravascular enhancement), compared to the standard injection protocol.
1 year
subjective image quality
Time Frame: 1 year
The performance of the individualised injection protocols in CCTA with regard to subjective image quality (4-point Likert scale), compared to the standard injection protocol.
1 year
Coronary artery disease
Time Frame: 1 year
To assess the presence and severity of coronary artery disease (CAD) with help of the CAD-RADS classification
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University Medical Center

Investigators

  • Principal Investigator: Joachim E Wildberger, Prof.dr., Maastricht University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 11, 2017

Primary Completion (ACTUAL)

September 14, 2018

Study Completion (ACTUAL)

September 14, 2018

Study Registration Dates

First Submitted

September 20, 2017

First Submitted That Met QC Criteria

September 20, 2017

First Posted (ACTUAL)

September 25, 2017

Study Record Updates

Last Update Posted (ACTUAL)

March 21, 2019

Last Update Submitted That Met QC Criteria

March 19, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL59507.068.16

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cardiac Disease

Clinical Trials on Contrast media administration

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mali

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe