Clinical trial NCT05700877: Screening and Intervention for Subclinical Coronary Artery Disease in Patients With Type 2 Diabetes
Official title: Screening and Intervention for Subclinical Coronary Artery Disease in Patients With Type 2 Diabetes: THE STENO INTEN-CT STUDY
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Type 2 Diabetes
Cardiovascular Diseases
Keywords: CVD screening
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2023-01-26
Enrollment: 7300
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Steno Inten-CT study is an investigator-initiated pragmatic open-label event-driven randomized controlled trial.
Primary purpose: PREVENTION

Brief summary: The investigators intend to perform a landmark study to answer whether a combined CVD screening and treatment strategy is beneficial for patients with type 2 diabetes (T2DM) without known cardiovascular disease (CVD)

The investigators aim to answer the following main research questions:

Do screening detected high-risk patients benefit of intensified medical treatment?

Is it safe to de-intensify medical treatment among patients with a screening detected low risk of CVD?

Does a CVD screening and treatment program improve patient reported health status?

Cardiovascular risk remains high in patients with T2DM but unevenly distributed. Our current risk stratification strategies are far from optimal leading to both under- and over-treatment of patients. In recent years, noninvasive imaging of subclinical coronary artery disease by cardiac CT has improved considerably. This allows for easily accessible evaluations of coronary atherosclerosis burden and composition - exceptionally strong imaging biomarkers of future cardiovascular disease. An increasing amount of data suggests that cardiac CT may permit better risk stratification in patients with T2DM. At the same time, the pharmaceutical treatment of T2DM has changed with several new and expensive drug classes, each individually documented to reduce the risk for new or recurrent cardiovascular events. Thus, these new drugs may improve outcome in high-risk patients, whereas they may be wasteful and only lead to side effects in low-risk patients.

In the Inten-CT study, the investigators combine these two pivotal developments. The investigators intend to improve risk stratification of patients with T2DM by use of cardiac CT and, based on this knowledge, the investigators wish to investigate if upgraded medical treatment in the high-risk population is beneficial and if de-intensified treatment in the low-risk population is safe. As a secondary aim, the investigators wish to investigate if such a strategy improves patient reported health status. These aims are in agreement with one of the important health indicators from The Danish College of General Practitioners: "We find and treat the patients and let the healthy stay healthy". The investigators intend with this strategy to improve not only cardiovascular outcome among patients with T2DM, but also their quality of life.

The Inten-CT study is an investigator-initiated open-label event-driven randomized controlled trial including patients with T2DM stratified according to screen detected coronary artery calcification. The investigators expect inclusion of 7300 patients in 2 years and a mean follow-up period of 5 years.

Detailed description: HYPOTHESES Intensified multifactorial treatment is superior to standard treatment in patients with CAC score ≥100.

Less intensive multifactorial treatment is non-inferior to standard treatment in patients with CAC =0.

AIMS Primary aim 1: Cardiovascular benefit In patients identified with high cardiovascular risk as indicated by a CAC score ≥100, the investigators aim to compare the effect of intensified multifactorial treatment versus standard treatment.

Primary aim 2: Cardiovascular safety In patients identified with low cardiovascular risk as indicated by a CAC score of zero, the investigators aim to compare the effect of less intensive multifactorial treatment versus standard treatment.

Secondary aim 1: Patient-reported outcomes the investigators aim to compare patient-reported outcomes in the CAC-based treatment group and the control group.

Secondary outcome: Quality adjusted life years (QALY) using data from the EQ-5D questionnaire and Danish preference weights of the normal population

Secondary aims 2: Cost-Effectiveness The investigators aim to compare costs and outcomes between the two groups after study completion.

Secondary aims 3: Treatment The investigators aim to quantify and compare the protocol-driven and symptom-driven diagnostic tests and therapeutic interventions between the intervention groups and control groups during the study period.

The investigators aim to evaluate the adherence and efficacy of the therapeutic interventions in the intervention groups and the control groups during the study period.

Secondary aims 5: Screening The investigators aim to evaluate the association of CAC score and coronary CT angiography derived measures of coronary atherosclerosis burden, respectively, and CVD prognosis in patients with T2DM.

The investigators aim to explore the association between CAC score, coronary CT angiography derived measures of coronary atherosclerosis burden and echocardiography derived measures of systolic/diastolic function. Specifically, the investigators aim to explore the ability of echocardiography to re-classify patients stratified by CAC and coronary CT angiography.

Secondary aims 6: Biomarkers The investigators aim to explore the association between CAC score, biochemical markers of inflammation and atherosclerosis (blood high-sensitivity C-reactive protein, IL-1ß, IL-6, sE-selectin, sICAM-1, sVCAM, osteopontin, osteoprotegrin and urinary proteomic risk classifier CKD273, CAD258, ACSP75, and HF1), and CVD prognosis in patients with T2DM.

METHODS Design The Steno Inten-CT study is an investigator-initiated pragmatic open-label event-driven randomized controlled trial.

First, a cardiac CT scan is performed in all participants. Next, patients are randomized to either continue standard diabetes treatment blinded to CT scan and CAC results or receive CAC-based treatment. Patients randomized to CAC-based treatment, will be stratified into low- or high-risk patients (defined by CAC score \<100 or ≥ 100), and hence, allocated to two parallel clinical studies. High-risk patients in the CAC-based treatment group will be included in a study in which they will receive information on CAC-score, mandatory treatment with dapagliflozin and semaglutide (both study drugs), and advise on further multifactorial treatment of blood lipid levels, blood pressure and antithrombotic therapy. Low-risk patients will be included in a study in which they receive advise on a potential downgrade in diabetes treatment (CAC =0).

Patients with CAC score 1-99 will be advised to follow contemporary guidelines in diabetes treatment and will not be included in the primary analyses (Primary aims 1 and 2).

At End of Study (determined by an independent outcome committee), CVD event rates will be compared between patients in the standard treatment group and the CAC-based treatment group, stratified according to their CAC-level (CAC ≥100, and CAC=0)

Eligibility criteria: Inclusion Criteria:

* New or former diagnosis of Type 2 diabetes according to WHO.
* Age between 55-69 years (men) and 60-74 years (women).
* Signed declaration of consent

Exclusion Criteria:

* Previous history of CVD (previous myocardial infarction or coronary intervention (percutaneous coronary intervention or by-pass), heart failure, stroke or peripheral artery disease as documented by the patient or the patient medical record).
* Contraindications or allergies to both SGLT2 inhibitors and GLP-1 analogues.
* Signs of critical cardiac disease: \>50% stenosis of left main coronary artery (CT angiography) or left ventricular ejection fraction below 30% (echocardiography). If a CT angiography is not available, a CAC\>1000 on the non-contrast cardiac CT will be considered equal to critical cardiac disease.
* Expected life duration \< 1 year for any reason.

Primary outcomes:
measure: Rates of a composite cardiovascular endpoint
timeFrame: Event-driven, expected mean follow-up of 5 years
Secondary outcomes:
measure: Rates of all-cause mortality and individual components of the primary outcome
timeFrame: Event-driven, expected mean follow-up of 5 years
measure: Patient reported outcomes 1
timeFrame: Change from baseline to End of Study (Event-driven, expected mean follow-up of 5 years)
measure: Patient reported outcomes 2
timeFrame: Change from baseline to End of Study (Event-driven, expected mean follow-up of 5 years)
measure: Patient reported outcomes 3
timeFrame: Change from baseline to End of Study (Event-driven, expected mean follow-up of 5 years)
measure: Cost-effectiveness
timeFrame: Event-driven, expected mean follow-up of 5 years
Other outcomes:
measure: Treatment with prespecified drugs
timeFrame: Event-driven, expected mean follow-up of 5 years
measure: Cardiovascular risk markers 1
timeFrame: Event-driven, expected mean follow-up of 5 years
measure: Cardiovascular risk markers 2
timeFrame: Event-driven, expected mean follow-up of 5 years
measure: Cardiovascular risk markers 3
timeFrame: Event-driven, expected mean follow-up of 5 years
measure: Cardiovascular risk markers 4
timeFrame: Event-driven, expected mean follow-up of 5 years
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Steno Diabetes Center Aarhus, AUH, and Aarhus University
name: Per L Poulsen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Axel Diederichsen, Professor
role: PRINCIPAL_INVESTIGATOR
References: