Clinical trial NCT05497466: PUMCH Study Into Individualized Scanning for Coronary Artery Disease
Official title: PUMCH Study Into Individualized Scanning for Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Coronary Computed Tomographic Angiography
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2022-08-11
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study aims to consecutively include 300 patients scheduled for coronary CTA examination to rule out CAD in PUMCH.

Brief summary: Cardiac computed tomographic angiography (CCTA) is a non-invasive diagnostic imaging technique for visualization of the coronary arteries and thus, frequently used in the evaluation of coronary artery disease (CAD). CT technology is improving continuously, and various technological advances not only increase diagnostic accuracy, but also provide a substantial reduction in radiation dose and scan acquisition time. These modifications challenge optimal synchronization and timing of scan protocols in CM administration due to a shorter data acquisition window, hereby creating opportunities for injection strategies with a decrease in total amount of contrast media (CM). \[4-6\] Reducing the radiation dose of CT angiography and injected CM dose have become a routine need and trend in clinical practice. In addition to this, physical factors such as cardiac output and body weight are considered important factors with regard to variability in vascular enhancement. A standard 'one size fits all' protocol with a standard injected CM volume, independent of weight and length of the patient has proven to be outdated and precision medicine in the future should be based on individually tailored scan and CM injection protocols that are more scientific and involve various parameters such as individual tube voltage, patients weight and heart rate to benefit patients by reducing radiation exposure and CM dose while fulfilling the diagnostic purpose.

Prospective studies focused on modifying both scan and injection parameters were completed in the Dutch (representing European) patient population with body weight varying between 40 and 130kg by Maastricht University Medical Center (MUMC) and have shown very promising results in Dutch population. In theory, these scan and injection protocols should be applicable to both average Dutch population (e.g. European population) and other heterogeneous patient populations, i.e. world-wide patient populations with any BMI category. However, so far, the effectiveness of this approach has not been deliberately discussed in the (on average) heavier North American population or the lighter Asian population. So, prior to promotion of the individually tailored CT scan protocols for global use, we need to obtain enough evidence in terms of the diagnostic confidence from those protocols in Chinese patients who could represent Asian population.

Detailed description: Primary objective: To prospectively evaluate the diagnostic quality (including the intravascular attenuation of the coronary arteries and image quality) in a previously validated individualized scan and CM injection CCTA protocol whereas both scan and injection parameters are tailored to the individual patient in Chinese population.

Secondary Objective(s):

1. To evaluate the radiation dose and contrast media dose of this individualized approach for CCTA in a Chinese patient population.
2. To evaluate the injection parameters required for the average patient population.

Subjects will be screened according to clinical data and enrolled in the study after providing informed consent. Patients will be scanned by Siemens Force CT scanner, prospective ECG gate-control and narrow window scanning technology, as well as intelligent KV (CARE-KV Tech) scanning technology. The CARE-kV software will determine optimal scan parameters for each patient, without any human intervention. By this means, each patient will be included in a specific tube-voltage arm based on in the condition of individual patient.

Care kV is a software that collects information about the patient's own attenuation values/ x-ray absorption during a so-called scout scan. Based on these parameters and taking into account the required scan quality (e.g. parenchymal, bone or vascular), the software determines the optimal scan settings for the patient. This includes both a variable tube current (in mAs) along the z-axis of the patient and an individual tube voltage (in kV). The tube voltage can be selected between 70 and 150kV in steps of 10kV. For this study, the scan quality slider will be set to 'vascular' or '11', which is commonly used in clinical studies and clinical practice for CCTA.

Iopromide injection (iodine concentration 370 mgI/ml) (Ultravist, Bayer Healthcare, Berlin, Germany) is administered as a bolus through the cubital vein using dual-syringe high-pressure injector (CT high-pressure injector: Stellant, MEDRAD, Pittsburg, PA, USA). The CM injection parameters are computed according to patient and examination-related parameters (patient weight, CM concentration, scan duration and maximum flow rate) using the Personalized Patients Protocol Technology (P3T) software supplied in the high-pressure injector.

P3T (Personalized Patient Protocol Technology) software computes individualized contrast injection protocols. P3T Cardiac/Pulmonary arteries are indicated for use with CAT of the cardiac structures, coronary arteries, chambers of the heart, pulmonary vasculature, thoracic and abdominal aorta. During initial setup, options such as minimum and maximum iodine loads, minimum injection duration, and other settings are configured according to site preferences and guidelines. These options are stored as a "preset", which can then be selected to calculate an injection protocol. At that time, patient and procedure specific parameters (patient weight, CM concentration, scan duration, and maximum flow rate) are entered by the radiographer. The software calculates the iodine load by multiplying the patient weight by a pre-determined dosing factor, applying the configured minimums and maximums. Then, the injection duration is determined based on the duration of the scan and minimum injection duration. Using the iodine load, injection duration, and CM concentration, the individualized flow rate and CM volumes are computed. The radiographer may edit the injection protocol if necessary. Dosing factors were derived based on pharmacokinetic model to simulate vascular enhancement in the regions of interest, targeting 350-400 HU across a wide range of patients.

An 18G or 20G venous access in the antecubital vein is preferred for higher flow rates. If low flow rates are required, venous access through an IV needle as small as 22G (max flow: 6.5 mL/sec) may be used.

* Test bolus + saline flush, next CM bolus and saline flush 40ml. Prewarmed (37 º C \[99˚F\]) CM (Iopromide 370mgI/ml, Bayer).
* Injection using a programmable dual-head CT injector (Stellant, Bayer), via an 18-20G intravenous injection catheter in the left or right antecubital vein. We propose to use the appropriate gauge for the expected flow rate, according to local safety regulations.
* P3T Cardiac Certegra/ Use patient body weight adjusted protocol: P3T Cardiac, Certegra. (This will show flow rates if one sets the injection time and contrast media concentration).
* Adjust for selected kV setting by adapting the IDR: -10% for 110kV, -20% for 100kV, -30% for 90kV, -40% for 80kV and -50% for 70kV.
* In all patients, a test bolus injection at the level of the ascending aorta is performed to assess optimal start delay; 20ml of CM at a flow rate according to P3T protocol. Test bolus is followed by 40ml of saline flush at the same flow rate.

Study archiving: patient protocol (radiation dose information), ECG information, contrast media information, scout views calcium score scan, heart scan (Bv40, 0.6mm slices).

For this study we chose to include 300 patients to ensure a representation of normal patient variance. Given the assumed non-diagnostic rate to be around 5%, the 95% CI of non-diagnostic rate with 300 sample size is \[2.8 %, 8.1%\]. Although there is no hypothesis test planned for this study, the result from a recent published study taking similar design on individualized scan and injection protocol of liver CT provides support on adequate sample size of the current study. Based on the study, 256 patients in total could enable the stratification performed based on age (\<60 and ≥60 years) and weight (\<75 and ≥75 kg) in the population weighed below 115 kg.

If 300 patients are not included after 18 months, the inclusion period will be over none the less.

Eligibility criteria: Inclusion Criteria:

* Age: Patient aged older than 18;
* Deny previous cardiovascular history；
* Atypical or typical complaints of angina and referred for CCTA to rule out CAD with Iopromide 370 mgI/ml by clinicians
* Possibility of 'flash' mode scan: patient heart rate below 70 beats per minute and regular rhythm；
* Patients or families are able to understand the study protocol and willing to participate in the study and provide written informed consent.

Exclusion Criteria:

* Any contraindications for prospective ECG gate-control CT coronary angiography, including：

  1. Inability to perform a breath hold for at least the expected scan time；
  2. Unstable angina；
  3. Hemodynamic instability；
  4. Pregnant or lactating women；
  5. Renal insufficiency (defined as eGFR\<30 ml/min/1.73m2);
  6. Previous history of adverse reactions to iodinated contrast agents；
  7. Confirmed or suspected hyperthyroidism or pheochromocytoma；
  8. Atrial fibrillation or arrhythmia; severe congestive heart failure (class IV according to NYHA classification of cardiac function)；
* History of CAD
* Patients undergoing PCI before coronary CTA examination, or patients with a previous history of heart bypass surgery
* Insufficient cannula venous access (preferred 18G, minimal 20G cannula)；
* Patients who are participating other clinical studies。

Primary outcomes:
measure: The diagnostic quality produced by individualized scan and injection protocol.
timeFrame: 48 hours post examination
Secondary outcomes:
measure: Objective evaluation on image quality
timeFrame: 48 hours post examination
measure: Subjective evaluation on image quality
timeFrame: 48 hours post examination
measure: contrast media dose in ml
timeFrame: During Injection procedure
measure: contrast media flow rate in ml/s
timeFrame: During Injection procedure
measure: contrast media peak flow rate [ml/s]
timeFrame: During Injection procedure
measure: Time-to-peak of contrast media [s]
timeFrame: During Injection procedure
measure: iodine delivery rate (IDR) in mgI/s
timeFrame: During Injection procedure
measure: Patient radiation dose:volume CT dose index (CTDIvol) in mGy
timeFrame: 48 hours post examination
measure: Patient radiation dose: size-specific dose estimates (SSDEs) of chest in mGy
timeFrame: 48 hours post examination
measure: Patient radiation dose: dose length product (DLP) in mGy*cm
timeFrame: 48 hours post examination
measure: Patient radiation dose: effective dose (ED) in mSv
timeFrame: 48 hours post examination
Other outcomes:
Locations:
Study officials:
affiliation: PUMCH
name: Zhengyu Jin
role: PRINCIPAL_INVESTIGATOR
References: