Evaluation of Diagnostic Accuracy, Safety, and Cost-Effectiveness of the Non-Invasive Cardiolens FFR-CT Pro Method to Measure the Fractional Flow Reserve in Diagnostics of Chronic Coronary Syndromes Versus the Standard Diagnostic Modalities.

Completed

• Conditions: Coronary Artery Disease; Stable Ischemic Heart Disease
• Interventions: Procedure: CCTA (Coronary Computed Tomography Angiography); Procedure: ICA (Invasive Coronary Angiography); Procedure: FFR (Fractional Flow Reserve); Device: CNBP measurement; Device: Cardiolens FFR-CT Pro

• Registration Number: NCT04777513
• Lead Sponsor: Hemolens Diagnostics Sp. z o.o.

Brief Summary

A multicentre, post-marketing, observational trial in 450 patients, whose standard diagnostic workup for chronic coronary syndromes provided for Invasive Coronary Angiography (ICA). Medical records of a potential subject of the trial before their enrolment contain a good quality result of at least 128-slice CCTA performed up to 3 months before the elective ICA. CCTA should find at least one ≥50% stenosis in at least one big coronary artery of ≥ 2 mm diameter. At one hour before ICA in the latest the patient should have a resting Continuous Non-Invasive Blood Pressure (CNBP) taken with a certified device delivered by LifeFlow. The last criterion before including a patient in the final analysis is at least one significant (≥50%) stenosis in one or two coronary arteries of ≥ 2 mm diameter visually confirmed by ICA with a FFR measurement taken in these arteries.

The data collection period will cover time from admission for the elective ICA to discharge from the hospital (evaluation of possible adverse events related to invasive procedures).

After initial qualification of available data by the attending physician, selected patients will be asked for a consent to participation in the trial no later than upon admission for the elective ICA and before CNBP measurement.

Detailed Description

Stage 1

After a patient declares their consent, a doctor or another member of the study team trained by the sponsor will perform procedures in the following order:

* Define the unique patient ID to be recorded in the CRF with the patient's demographic data

* Assess the quality of CCTA imaging data (DICOM) according to guidelines agreed upon with the sponsor and record the number and location of the significant (≥50%) stenosis sites in the CRF based on CCTA

* No later than one hour before ICA starts, perform a physical examination consisting in instantaneous peripheral blood pressure (systolic and diastolic) resting measurement performed with a standard sphygmomanometer and Continuous Non-Invasive Blood Pressure measurement (1-3 min).

Stage 2

After the procedures mentioned above are performed, the patient will undergo elective ICA with the outcomes, i.e.:

* video material showing the location of the wire during the FFR measurement,

* digital pressure signals exported from the FFR measuring device used to determine the value of the invasive FFR,

* values of FFR measurements obtained during ICA will be entered after being anonymised in a dedicated HEMOFLOW PMS_2020 reference database.

Stage 3

Within 48 hours of ICA completion a doctor or another member of the study team trained by the sponsor:

* will enter the following data in the Cardiolens FFR-CT Pro system:

1. Patient's data, i.e. patient's ID, gender, height, body mass, exercise tolerability, information on used medications and smoking cigarettes. Optionally, i.e. if upon admission for ICA a blood test was performed as a part of the standard diagnostic workup - haematocrit levels and total protein concentration

2. Files containing CCTA imaging data in the DICOM format.

3. Values of instantaneous peripheral blood pressure (systolic and diastolic) resting measurement performed with a standard sphygmomanometer as well as the digital signal obtained during the CNBP measurement (1-3 min)

* Based on the CCTA description or meta data contained in the imaging data the doctor or another member of the study team will record the following information in the CRF:

1. Radiation dose during CCTA

2. Contrast medium dose during CCTA

* Will enter the following information in the CRF:

1. Radiation dose during the diagnostic part of ICA

2. Contrast medium dose during the diagnostic part of ICA

3. Number and type of adverse events

4. Duration of the diagnostic workup.

Stage 4

Within 7 days of entering all the stage 3 data the investigator (a cardiologist) trained by the sponsor will measure the value of the virtual FFR with the Cardiolens FFR-CT Pro system at locations corresponding to ICA FFR measurements (based on video recording entered in the database during stage 2)

Based on results obtained from the Cardiolens FFR-CT Pro system vs reference data an analysis will be performed on meeting the primary and secondary end points of the trial.

Study Timeline

• Study Start: 2020-08-06
• Study First Submitted: 2021-02-08
• Study First Submitted QC: 2021-03-01
• Study First Posted: 2021-03-02
• Primary Completion: 2022-09-30
• Study Completion: 2023-05-31
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. Age ≥ 18

2. Declaration of informed consent to sharing medical records gathered during the standard diagnostic workup

3. History of chronic coronary syndromes (CCS)

4. Diagnostic CCTA (good quality test allowing investigation of the entire coronary artery tree), showing at least one site with stenosis ≥50% of the lumen in a large coronary artery of ≥ 2 mm diameter, with no prior revascularisation

5. Standard treatment of chronic coronary syndromes with no dosage modification required within at least 4 weeks before the enrolment

6. Patients with a prior acute coronary syndrome (ACS) or revascularisation would be found eligible under the following conditions:

   • Over 30 days from the acute coronary syndrome occurrence
   • FFR assessment during ICA may only cover the vessels that were not revascularized (both PCI and CABG) and were not the reason of ACS
   • No closed coronary arteries

Exclusion Criteria

1. CCTA-confirmed myocardial bridges causing >50% stenosis of the epicardial vascular lumen
2. Coronary obstruction confirmed by CCTA or invasive coronarography
3. History of ACS with coronary angioplasty or Coronary Artery Bypass Grafting (CABG) performed unless point 6 conditions are met
4. Significant haemodynamic abnormalities of the valve or history of surgical correction of the defect or CABG
5. Second-degree or third-degree atrioventricular block, sinus node dysfunction, QTc > 450 ms or prolonged QTc
6. LVEF ≤ 35% found in an echocardiogram performed within the last 6 months
7. BMI ≥ 35
8. Clinically apparent infection
9. Thrombocytopenia below 100.000/mm3
10. Active neoplastic disease (apart from basal cell carcinoma and carcinoma in situ) and other conditions, which, in the investigator's opinion significantly affect their life expectancy
11. Other significant conditions, infections, addictions and psychological or social factors, which, in the doctor's opinion, may affect patient's ability to participate in the trial or significantly affect their safety

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Standard of care: FFR, ICA, CCTA	CCTA (Coronary Computed Tomography Angiography)	Patients with medical history for ischaemic heart disease will take part in non-invasive determination of haemodynamic parameters in coronary arteries with Cardiolens FFR-CT Pro technology.
Standard of care: FFR, ICA, CCTA	Cardiolens FFR-CT Pro	Patients with medical history for ischaemic heart disease will take part in non-invasive determination of haemodynamic parameters in coronary arteries with Cardiolens FFR-CT Pro technology.
Standard of care: FFR, ICA, CCTA	ICA (Invasive Coronary Angiography)	Patients with medical history for ischaemic heart disease will take part in non-invasive determination of haemodynamic parameters in coronary arteries with Cardiolens FFR-CT Pro technology.
Standard of care: FFR, ICA, CCTA	FFR (Fractional Flow Reserve)	Patients with medical history for ischaemic heart disease will take part in non-invasive determination of haemodynamic parameters in coronary arteries with Cardiolens FFR-CT Pro technology.
Standard of care: FFR, ICA, CCTA	CNBP measurement	Patients with medical history for ischaemic heart disease will take part in non-invasive determination of haemodynamic parameters in coronary arteries with Cardiolens FFR-CT Pro technology.

Primary Outcome Measures

Name	Time	Method
The evaluation of the increased diagnostic accuracy of the non-invasive Cardiolens FFR-CT Pro technology	Up to 18 months	Evaluation of the increased diagnostic accuracy (area under ROC curve, AUC) in detection of haemodynamically significant stenoses in coronary arteries with a non-invasive Cardiolens FFR-CT Pro technology compared to CCTA in reference to the invasive fractional flow reserve (FFR) testing at the arterial level.

Secondary Outcome Measures

Name	Time	Method
The evaluation of safety of the non-invasive Cardiolens FFR-CT Pro technology	Up to 5 days. The date from admission for the scheduled ICA to discharge from the hospital.	Evaluation of safety of the non-invasive Cardiolens FFR-CT Pro technology (the result of the non-invasive test completes the diagnostic workup for coronary disease) compared to the standard diagnostics in chronic coronary syndromes based on the following parameters: 1. Radiation dose during the diagnostic workup; 2. Contrast medium dose in the diagnostic workup; 3. Adverse events during the diagnostic workup; 4. Duration of the diagnostic workup
The evaluation of diagnostic accuracy of the non-invasive Cardiolens FFR-CT Pro technology	Up to 18 months	Evaluation of diagnostic accuracy of Cardiolens FFR-CT Pro in detection of haemodynamically significant stenoses in coronary arteries (FFR value ≤0.80) compared to CCTA (stenosis ≥ 50%), in reference to the invasive FFR testing at the patient and arterial level, based on parameters like sensitivity, specificity, positive/negative predictive value, accuracy at the patient and arterial level.
The evaluation of the costs of Cardiolens FFR-CT Pro technology	Up to 5 days. The date from admission for the scheduled ICA to discharge from the hospital.	3) Evaluation of the costs of Cardiolens FFR-CT Pro in diagnostics of chronic coronary syndromes compared to the standard diagnostic workup (the sum of the costs for individual diagnostic modalities according to the National Health Fund reimbursement prices as well as Procedural Reimbursement Payment Guide)

Trial Locations

Locations (11)

American Heart of Poland, Centrum Kardiologii i Kardiochirurgii w Bielsku-Białej; 🇵🇱 Bielsko-Biala, Poland

Oddział Kliniczny Kardiologii oraz Interwencji Sercowo-Naczyniowych Szpital Uniwersytecki w Krakowie; 🇵🇱 Cracovia, Poland

The Cardinal Stefan Wyszyński National Institute of Cardiology; 🇵🇱 Warsaw, Poland

American Heart of Poland, Centrum Sercowo - Naczyniowe w Ustroniu; 🇵🇱 Ustroń, Poland

The Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University; 🇵🇱 Katowice, Poland

"Miedziowe Centrum Zdrowia" S.A.; 🇵🇱 Lubin, Poland

The 4th Military Teaching Hospital; 🇵🇱 Wrocław, Poland

The University Clinical Centre; 🇵🇱 Gdańsk, Poland

The John Paul II Specialist Hospital in Cracovia; 🇵🇱 Cracovia, Poland

The Jan Mikulicz-Radecki University Teaching Hospital; 🇵🇱 Wrocław, Poland

The T. Marciniak Lower Silesian Specialist Hospital - Center of Emergency Medicine; 🇵🇱 Wrocław, Poland