Screening and Intervention for Subclinical Coronary Artery Disease in Patients With Type 2 Diabetes

Cardiovascular Diseases Clinical Trial

— STENO INTEN-CT  

Official title:

Screening and Intervention for Subclinical Coronary Artery Disease in Patients With Type 2 Diabetes: THE STENO INTEN-CT STUDY

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05700877
• Other study ID #: 2022-500143-21-01
• Status: Recruiting
• Phase: Phase 4
• Start date: January 26, 2023
• Est. completion date: March 1, 2029

Study information

• Verified date: January 2023
• Source: University of Aarhus
• Contact: Kristian L Funck, MD PhD
• Phone: +4561331588
• Email: klf[@]clin.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7300
• Est. completion date: March 1, 2029
• Est. primary completion date: January 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Myocardial Ischemia
• Type 2 Diabetes

Intervention

Other:
• CAC-based treatment strategy
The intervention is a combination of screening with a heart CT scan and multifactorial intervention based on the screening results. Participants randomized to CAC-based treatment and with screening results showing high risk of CVD, will receive a multifactorial intervention including the combination of two open label investigational medical products: dapagliflozin 10mg/day and semaglutide 0.25 /week or 0.5 /week or 1.0 /week.
• Standard treatment
Participants randomized to standard treatment are recommended to follow updated guidelines for CVD prevention.

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense

Sponsors (2)

Lead Sponsor	Collaborator
Per Løgstrup Poulsen	Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment with prespecified drugs	Treatment with prespecified CVD prophylactic drugs will be recorded through the national health registries. Treatment initiation will be registered.	Event-driven, expected mean follow-up of 5 years
Other	Cardiovascular risk markers 1	Lipid levels (total cholesterol, LDL, HDL and triglycerides) collected in LABKA. Reported as mmol/l	Event-driven, expected mean follow-up of 5 years
Other	Cardiovascular risk markers 2	Office blood pressure (mmHg) collected in Dansk Voksen Diabetes Databasen.	Event-driven, expected mean follow-up of 5 years
Other	Cardiovascular risk markers 3	Body mass index (kg/m2) collected in Dansk Voksen Diabetes Databasen.	Event-driven, expected mean follow-up of 5 years
Other	Cardiovascular risk markers 4	Smoking cessation (number and percentage) collected in Dansk Voksen Diabetes Databasen.	Event-driven, expected mean follow-up of 5 years
Primary	Rates of a composite cardiovascular endpoint	Cardiovascular death, non-fatal myocardial infarction, hospitalization for heart failure, and non-fatal stroke	Event-driven, expected mean follow-up of 5 years
Secondary	Rates of all-cause mortality and individual components of the primary outcome	Individual components of the primary outcome consist of cardiovascular death, non-fatal myocardial infarction, hospitalization for heart failure, and non-fatal stroke	Event-driven, expected mean follow-up of 5 years
Secondary	Patient reported outcomes 1	EQ5D questionnaire with the outcome of a EQ5D-score	Change from baseline to End of Study (Event-driven, expected mean follow-up of 5 years)
Secondary	Patient reported outcomes 2	PHQ-9 questionnaire with the outcome of a PHQ-9-score	Change from baseline to End of Study (Event-driven, expected mean follow-up of 5 years)
Secondary	Patient reported outcomes 3	GAD-7 questionnaire with the outcome of a GAD-7-score	Change from baseline to End of Study (Event-driven, expected mean follow-up of 5 years)
Secondary	Cost-effectiveness	Cost per quality adjusted life years (QALY)	Event-driven, expected mean follow-up of 5 years