Screening Of CoRonary ArTEry diSease

Coronary Artery Disease Clinical Trial

— SOCRATES  

Official title:

Medico-economic Evaluation of a Strategy With Coronary CT as First Line (CCTA) Compared With the Strategy With Functional Test as First Line, in Patients at Intermediate Risk of Developing Stable Coronary Disease.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05369728
• Other study ID #: 2022-A00302-41
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2022
• Est. completion date: October 2026

Study information

• Verified date: April 2022
• Source: University Hospital, Grenoble
• Contact: Laura Chambon
• Phone: 04 76 76 89 35
• Email: lchambon[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized trial with the objective of comparing the cost-effectiveness of the 2 recommended strategies: CCTA vs functional tests, allowing the evaluation of the quality of life of these patients in relation to the health resources used. In symptomatic patients with an intermediate probability of having stable CAD, i.e., whose pretest or clinical probability does not allow the elimination of the disease, and in patients without anginal symptoms for low levels of exercise who do not respond to medical therapy, in France, the diagnostic care pathways have become mature enough to set up a pragmatic prospective randomized trial with the objective of comparing the cost-effectiveness of the 2 recommended strategies: CCTA vs. Probabilistic medico-economic reasoning makes it possible to establish this two-way hypothesis more easily than in clinical research without the need to impose the superiority of one of the strategies.

Description:

In Europe, cardiovascular disease remains the leading cause of death with 4 million deaths per year, of which 1.8 million are due to coronary heart disease (CHD). CAD also has a cost with 46 billion / year spent for its management. In France, 4 billion are spent on it, which shows that it remains a public health problem and that most of the premature events are avoidable, in particular by screening patients with symptoms that make them suspect it. In these symptomatic patients suspected of having CAD, screening is carried out in particular through the use of imaging with technological innovations and performances that are constantly being improved and validated in large randomized trials. The PROMISE trial randomized an impressive number of 10003 patients comparing coronary computed tomography angiography (CCTA) and functional testing to assess suspected CAD, which showed similar efficacy of the 2 strategies in terms of major adverse cardiovascular events (MACE) at 2 years: 3.3% for CCTA and 3% for functional testing. Thus, the 2019 European guidelines allow CCTA or functional testing as the initial test to diagnose CAD in symptomatic patients. Thus, clinicians now have 2 first-line strategies: CCTA or functional tests (myocardial scintigraphy, echocardiography, MRI). The clinician can choose to initiate management with an anatomic evaluation of the coronary arteries (CCTA) or a search for ischemia (functional test). These two ways of assessing CAD are very different and are the subject of debate in Europe. For example, the National Institute of Health and Care Excellence (NICE) in the United Kingdom now recommends CCTA as the first test, unlike in Europe. In view of all these arguments, it is relevant to propose a randomized trial with the objective of comparing the cost-effectiveness of the 2 recommended strategies: CCTA vs. functional tests, making it possible to evaluate the quality of life of these patients in relation to the health resources used. In symptomatic patients with an intermediate probability of having stable CAD, i.e., whose pretest or clinical probability does not allow the elimination of the disease, and in patients without anginal symptoms for low levels of exercise who do not respond to medical therapy, in France, the diagnostic care pathways have become mature enough to set up a pragmatic prospective randomized trial with the objective of comparing the cost-effectiveness of the 2 recommended strategies: CCTA vs. Probabilistic medico-economic reasoning makes it possible to establish this two-way hypothesis more easily than in clinical research without the need to impose the superiority of one of the strategies.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 800
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients aged 18 to 75 years
• Symptomatic patient in whom CAD cannot be excluded by clinical evaluation alone :

patient with a pre-test or "intermediate" clinical probability indicating imaging test according to European recommendations

• Patient affiliated to the social security system or beneficiary of such a system
• Written informed consent

Exclusion Criteria:

• Pre-test probability "low" < 5% or 5-15% without additive pejorative factors
• Clinical probability of "high" CAD, defined by symptoms typical of low exercise levels not responding to medical therapies
• Known history of CAD
• Severe impairment of left ventricular ejection fraction < 40%.
• Known chronic renal failure not on dialysis (GFR <30 ml / min /1.73 m²)
• Patient considered unfit for the study according to the investigator's judgement and in particular the impossibility of performing an anatomical and/or functional test of ischemia of the coronary disease
• Patient in a period of exclusion for another study
• Persons referred to in articles L1121-5 to L1121-8 of the public health code
• Patient participating in another interventional research

Related Conditions & MeSH terms

• Cardiology
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Other:
• Coronary CT in 1st line compared to the strategy with functional test in 1st line in patient at Intermediate Risk of Developing Stable Coronary Disease:
Coronary CT in 1st line compared to the strategy with functional test in 1st line in Patients at Intermediate Risk of Developing Stable Coronary Disease:

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

References & Publications (4)

Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. Erratum in: Eur Heart J. 2020 Nov 21;41(44):4242. — View Citation

Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, Ahmed M, Aksut B, Alam T, Alam K, Alla F, Alvis-Guzman N, Amrock S, Ansari H, Ärnlöv J, Asayesh H, Atey TM, Avila-Burgos L, Awasthi A, Banerjee A, Barac A, Bärnighausen T, Barregard L, Bedi N, Belay Ketema E, Bennett D, Berhe G, Bhutta Z, Bitew S, Carapetis J, Carrero JJ, Malta DC, Castañeda-Orjuela CA, Castillo-Rivas J, Catalá-López F, Choi JY, Christensen H, Cirillo M, Cooper L Jr, Criqui M, Cundiff D, Damasceno A, Dandona L, Dandona R, Davletov K, Dharmaratne S, Dorairaj P, Dubey M, Ehrenkranz R, El Sayed Zaki M, Faraon EJA, Esteghamati A, Farid T, Farvid M, Feigin V, Ding EL, Fowkes G, Gebrehiwot T, Gillum R, Gold A, Gona P, Gupta R, Habtewold TD, Hafezi-Nejad N, Hailu T, Hailu GB, Hankey G, Hassen HY, Abate KH, Havmoeller R, Hay SI, Horino M, Hotez PJ, Jacobsen K, James S, Javanbakht M, Jeemon P, John D, Jonas J, Kalkonde Y, Karimkhani C, Kasaeian A, Khader Y, Khan A, Khang YH, Khera S, Khoja AT, Khubchandani J, Kim D, Kolte D, Kosen S, Krohn KJ, Kumar GA, Kwan GF, Lal DK, Larsson A, Linn S, Lopez A, Lotufo PA, El Razek HMA, Malekzadeh R, Mazidi M, Meier T, Meles KG, Mensah G, Meretoja A, Mezgebe H, Miller T, Mirrakhimov E, Mohammed S, Moran AE, Musa KI, Narula J, Neal B, Ngalesoni F, Nguyen G, Obermeyer CM, Owolabi M, Patton G, Pedro J, Qato D, Qorbani M, Rahimi K, Rai RK, Rawaf S, Ribeiro A, Safiri S, Salomon JA, Santos I, Santric Milicevic M, Sartorius B, Schutte A, Sepanlou S, Shaikh MA, Shin MJ, Shishehbor M, Shore H, Silva DAS, Sobngwi E, Stranges S, Swaminathan S, Tabarés-Seisdedos R, Tadele Atnafu N, Tesfay F, Thakur JS, Thrift A, Topor-Madry R, Truelsen T, Tyrovolas S, Ukwaja KN, Uthman O, Vasankari T, Vlassov V, Vollset SE, Wakayo T, Watkins D, Weintraub R, Werdecker A, Westerman R, Wiysonge CS, Wolfe C, Workicho A, Xu G, Yano Y, Yip P, Yonemoto N, Younis M, Yu C, Vos T, Naghavi M, Murray C. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017 Jul 4;70(1):1-25. doi: 10.1016/j.jacc.2017.04.052. Epub 2017 May 17. — View Citation

Timmis A, Townsend N, Gale CP, Torbica A, Lettino M, Petersen SE, Mossialos EA, Maggioni AP, Kazakiewicz D, May HT, De Smedt D, Flather M, Zuhlke L, Beltrame JF, Huculeci R, Tavazzi L, Hindricks G, Bax J, Casadei B, Achenbach S, Wright L, Vardas P; European Society of Cardiology. European Society of Cardiology: Cardiovascular Disease Statistics 2019. Eur Heart J. 2020 Jan 1;41(1):12-85. doi: 10.1093/eurheartj/ehz859. Erratum in: Eur Heart J. 2020 Dec 14;41(47):4507. — View Citation

Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016 Jan 26;133(4):e38-360. doi: 10.1161/CIR.0000000000000350. Epub 2015 Dec 16. Erratum in: Circulation. 2016 Apr 12;133(15):e599. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Conduct a cost-utility analysis (CUA) comparing the strategy "CCTA in 1st line" to the strategy "functional test in 1st line" in patients with suspected stable CAD in a collective perspective, at 1 year.	The incremental cost-utility ratio (ICER) will be calculated by relating the difference in costs to the difference in the average number of QALYs. The ratio will therefore be expressed as cost per QALY gained, which represents the additional cost of gaining one year of healthy life with the "CCTA" strategy vs. the "functional test" strategy. Since CCTA is a special case of CEA, the incremental cost-effectiveness ratio (ICER) expressed as the incremental cost per life-year gained will also be calculated.	1 year
Secondary	To model in the long term (10 years) the impact of the 2 diagnostic strategies in terms of cost and consequences as defined in the main objective.	Incremental cost-effectiveness ratio (ICER and ICER) at 10 years as defined in Primary Objective 1.	10 years
Secondary	Conduct a budget impact analysis (BIA) from the National Health System's perspective at 3 and 5 years.	Measure the financial impact on the National Health System of the deployment of the CCTA strategy in 3 and 5 years	3 and 5 years
Secondary	To compare angina symptoms (limitation, stability, frequency) at 1 year.	SAQ (Seattle Angina Questionnaire): physical limitation is assessed by question 1; angina stability by question 2 and angina frequency by questions 3 and 4	1 year
Secondary	Compare treatment satisfaction at 1 year	SAQ: patients' satisfaction with their current treatment is assessed in questions 5 to 8	1 year
Secondary	Compare quality of life at 1 year	SAQ: quality of life is assessed in questions 9 to 11 of the questionnaire	1 year
Secondary	Compare dyspnea at 1 year	ROSE dyspnea scale : grade 1 to 4 (worst condition)	1 year
Secondary	Compare severity of angina at 1, 2 and 3 years	CCS score (Canadian Cardiovascular Society) : grade asymptomatic to 4 (worst condition)	1, 2 and 3 years
Secondary	Compare quality of life at 1, 2 and 3 years	Quality of life: EuroQol 5D-5 : cotation from 0 (worst condition) to 1.	1, 2 and 3 years
Secondary	Compare the care pathways of the "CCTA" strategy to the "Functional Test" strategy at 1 year.	Number of CAD imaging tests	1 year
Secondary	Compare the care pathways of the "CCTA" strategy to the "Functional Test" strategy at 1 year.	Time to obtain CAD imaging tests	1 year
Secondary	Compare the care pathways of the "CCTA" strategy to the "Functional Test" strategy at 1 year.	Type of CAD imaging tests	1 year
Secondary	Compare the care pathways of the "CCTA" strategy to the "Functional Test" strategy at 1 year.	Treatments used after the first line examination to manage chest pain symptomatology	1 year
Secondary	Observe deviations in management from current recommendations at 1 year.	Number and percentage of deviations from current recommendations	1 year
Secondary	Compare the diagnostic benefit of the CCTA strategy to the Functional Test strategy at 1 year.	Number and rate of coronary angiography with or without FFR/iwFR	1 year
Secondary	Compare the diagnostic benefit of the CCTA strategy to the Functional Test strategy at 1 year.	Number and rate of revascularization	1 year
Secondary	Compare major clinical events at 1, 2 and 3 years.	Deaths from cardiovascular causes, myocardial infarction, or ischemia-guided revascularization, heart failure, or recovered cardiac arrest.	1, 2 and 3 years.
Secondary	Compare the radiation exposure of patients for each strategy at 1 year.	Measurement of radiation exposure related to cardiovascular tests and procedures in millisieverts	1 year
Secondary	To study the influence of new indexes from post image processing on the consumption of care and on the symptoms of angina.	New indexes from post image processing	1 year
Secondary	To study the influence of new indexes from post image processing on the consumption of care and on the symptoms of angina.	QUALY	1 year
Secondary	To study the influence of new indexes from post image processing on the consumption of care and on the symptoms of angina.	SAQ (Seattle Angina questionnaire) question 1 to 19	1 year