Cost-effectiveness and Safety of the CADScorSystem in Patients With Symptoms Suggestive of Stable Coronary Artery Disease.

Angina, Stable Clinical Trial

— FILTER-SCAD  

Official title:

A Prospective, Randomized, Controlled, Parallel-group, Multicentre Trial to Examine the Cost-effectiveness and Safety of Adding the CADScorSystem as a Rule-out Test in Patients Referred With Symptoms Suggestive of Stable Coronary Artery Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04121949
• Other study ID #: FILTER-SCAD
• Status: Completed
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: September 15, 2023

Study information

• Verified date: October 2023
• Source: Bispebjerg Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the addition of the CADScorSystem to a standard Diamond-Forrester score guided rule-out strategy in ambulatory patients referred with symptoms suggestive of stable coronary artery disease. Half of the patients will undergo stratification using a Diamond-Forrester score only, while the other half will undergo stratification using a Diamond-Forrester score and a CAD-score. The study hypothesis is that the addition of a CAD-score will reduce unnecessary testing without compromising patient safety.

Description:

Purpose and Rationale for the Study:

The declining incidence of obstructive CAD and a good prognosis for patients with stable angina challenges the resource demanding approach recommended in current guidelines. The CADScor®System may be an efficient, fast and low-cost diagnostic tool with a high rule-out efficiency. The current study aims to investigate if the CADScor®System can be added as a rule-out test in patients referred with suspected stable CAD to reduce unnecessary testing

Study Hypothesis:

A Diamond-Forrester score plus CAD-score guided rule-out strategy is superior to a Diamond-Forrester score guided strategy alone in reducing diagnostic procedures and non-inferior in terms of safety outcomes in patients with symptoms suggestive of stable coronary artery disease.

Study Setting:

This study will enrol patients without known CAD who are referred with symptoms suggestive for stable CAD for outpatient evaluation at the participating sites. All patients will be symptomatic and require evaluation for suspected CAD. Thus, whether or not the patient chooses to participate in the study, the patient will undergo evaluation for suspected CAD. All the standard NIT modalities and ICA in the study are clinically well established and performed routinely and safely. Experimental testing involves the CADScor®System, for ruling out CAD before any NIT in the intervention group.

End of Study:

The study will end when all the following have occurred: (1) at least 2000 patients have been randomized, and (2) 12±1 months (1 year) have elapsed since the last patient was randomized.

Extended Follow-up after Study Termination:

Follow-up might be performed for up to 10 years after randomization. Follow-up information will be extracted from national registers, including information on cardiovascular events and treatments, hospitalizations and ambulatory visits due to cardiovascular events, and causes of death.

Statistical methods:

A detailed description of the planned statistical analyses will be documented in a separate statistical report and analysis plan (SAP), which will be completed before data base lock.

Sample size considerations:

A reduction of 15% or more in the primary endpoint is regarded as clinically significant. Assuming an alpha significance level of 0.05, a statistical power of 80% and an expected number of NIT/ICA of 0.94 per patient in the standard care group, a sample size of 314 patients in each arm is needed to ascertain superiority of the intervention.

A sample size of 1914 provides 90% power for testing non-inferiority in terms of MACE between the two testing strategies, at an alpha significance level of 0.05.

We choose to include 2000 patients, i.e. 1000 patients in each group, allowing for a 4% loss to follow-up and drop out and providing power for the primary endpoint and the secondary MACE non-inferiority endpoint.

Statistical analysis:

The full analysis set (FAS) will include all randomized patients in whom written informed consent was obtained and in accordance with the intention-to-treat principle all patients will be analysed according to the allocated treatment group.

The per-protocol set (PPS) will include only those patients from the FAS who did not have one of the following major protocol violations: inclusion criteria not met, exclusion criteria met, no DF-score calculation, or no CAD-score measurement (intervention group only). Patients who did not receive the randomly allocated CAD-score measurement will be included and analysed in the control group (per protocol analysis).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2016
• Est. completion date: September 15, 2023
• Est. primary completion date: September 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

1. Have signed the informed consent form.

2. Males and females, aged 30 years or above.

3. Be able and willing to comply with the clinical investigational plan.

4. Symptoms suggestive of stable coronary artery disease.

5. No history of coronary artery disease (prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft).

Exclusion Criteria:

1. Diamond-Forrester score >85%.

2. Prior non-invasive testing for stable CAD or invasive coronary angiography within 6 months of randomization.

3. Implanted donor heart, mechanical heart, mechanical heart pump.

4. Pacemaker or Cardioverter Defibrillator (ICD).

5. Implanted electronic equipment in the area above and around the heart.

6. Significant operation scars, abnormal body shape, fragile or compromised skin in the fourth left intercostal space recording area.

7. Receiving same day treatment with nitro-glycerine on the day of randomization.

8. Pregnancy.

The exclusion criteria '1. Diamond-Forrester score >85%' was removed after updating the study according to the 2019 ESC guidelines on chronic coronary syndrome. According to these current guidelines, no patients should be referred to invasive diagnostic test based on their PTP alone, and therefore is this exclusion criteria is no longer relevant.

Related Conditions & MeSH terms

• Angina, Stable
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Device:
• CADScor®System
The CADScor®System is a low cost, low resource-demanding, non-invasive, radiation-free device using highly advanced analysis of sounds originating from blood flow turbulence in the coronary circulation and myocardial motion. Heart sound recordings are obtained transcutaneously during a 3 minutes recording period with a microphone mounted at the IC4. A CAD-score on a scale from 0 to 99 is estimated immediately after the recording with a fully automated algorithm. The algorithm measures eight acoustic properties and the resulting acoustic score is combined with the clinical risk factors gender, age, and hypertension. The entire procedure lasts approximately 10 minutes.

Locations

Country	Name	City	State
Denmark	Amager Hospital	Copenhagen S
Denmark	University Hospital Herlev and Gentofte	Herlev
Denmark	University Hospital Nordsjaelland	Hillerød
Denmark	University Hospital Hvidovre	Hvidovre
Denmark	University Hospital Bispebjerg and Frederiksberg	København NV
Sweden	Skane University Hospital	Lund

Sponsors (6)

Lead Sponsor	Collaborator
Bispebjerg Hospital	Acarix, Kai Hansen Foundation, Kai Houmann Nielsens Fond, Larix A/S, Region Hovedstadens Apotek

Countries where clinical trial is conducted

Denmark,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in chest pain	Change in chest pain from baseline as assessed by the Seattle Angina Questionnaire (SAQ).	3 months and 1 year
Other	Change in quality of life	Change in quality of life from baseline as assessed by the EuroQoL-5D.	3 months and 1 year
Other	First non-invasive tests	Difference between the two treatment groups in the number of first non-invasive testings.	1 year
Other	Downstream tests	Difference between the two treatment groups in the number of downstream tests. Downstream tests are defined as all NITs and ICAs to detect CAD performed after a) DF-score and first standard non-invasive testing and b) DF-score, CAD-score and first non-invasive testing, respectively, in the two groups.	1 year
Other	Invasive coronary angiographies (ICA)	Difference between the two treatment groups in the number of invasive coronary angiographies.	1 year
Other	Negative invasive coronary angiographies	Difference between the two treatment groups in the number of negative invasive coronary angiographies.	1 year
Other	Repeat referrals	Difference between the two treatment groups in the number of repeat referrals.	1 year
Other	Time to rule-out CAD	Difference between the two treatment groups in time to rule-out CAD. Time to rule-out is assessed as the period from randomisation until the first test that rules out stable CAD.	1 year
Other	Time to diagnosis of CAD	Difference between the two treatment groups in time to diagnosis of CAD. Time to diagnosis is assessed as the period from randomisation until the first test that leads to the final diagnosis.	1 year
Other	Change in lifestyle measures	Change in lifestyle measures from baseline as assessed by the HeartDiet questionnaire.	3 months and 1 year
Other	Optimal medical treatment	Difference between the two treatment groups in the proportion of patients initiating and adhering to optimal medical treatment (event prevention, antianginal therapy).	1 year
Other	Incidence of individual components of MACE	Difference between the two treatment groups in the proportion of each of the individual components of major adverse cardiac events (all-cause death, myocardial infarction, unstable angina pectoris, heart failure, ischaemic stroke).	1 year
Other	Cumulative contrast dose	Difference between the two treatment groups in the cumulative contrast dose.	1 year
Other	Cumulative radiation dose	Difference between the two treatment groups in the cumulative radiation dose.	1 year
Other	Bleedings requiring hospitalization	Difference between the two treatment groups in the proportion of bleedings requiring hospitalization.	1 year
Other	Adverse events	Difference between the two treatment groups in the proportion adverse events related to the CADScor®System.	1 year
Primary	Cumulative number of non-invasive and invasive diagnostic procedures	Difference between the two treatment groups in cumulative number of non-invasive and invasive diagnostic procedures. Non-invasive procedures include exercise electrocardiogram (ECG), cardiac computed tomography angiography (CCTA), Rubidium cardiac PET (Rb-PET), myocardial perfusion imaging (MPI), cardiac magnetic resonance imaging (CMRi) and stress echocardiography. Invasive procedures include invasive coronary angiography (ICA) only.	1 year
Secondary	Incidence of Major adverse cardiac events (MACE)	Difference between the two treatment groups in proportion of major adverse cardiac events. Major adverse cardiac events (MACE) are a composite of all-cause death, non-fatal myocardial infarction, unstable angina pectoris, heart failure, and ischaemic stroke.	1 year