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

NCT ID: NCT05700877

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 7300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-12
• Study Completion Date: 2029-03-01

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)

Conditions

Type 2 Diabetes; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

CAC-based treatment

Patients randomized to CAC-based treatment, will be stratified into low- or high-risk patients (defined by CAC score=0 or ≥ 100), and hence, allocated to two parallel l clinical studies.

High-risk patients (CAC≥ 100) 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 (CAC=0) will be included in a study in which they will receive information on CAC-score and advise on how multifactorial treatment may be de-intensified.

Group Type: EXPERIMENTAL

CAC-based treatment strategy

Intervention Type: OTHER

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

Patients randomized to standard treatment and their primary physician are not informed about the screening findings. Patients are encouraged to follow contemporary diabetes guidelines at the time of inclusion. This information will be given in a written letter within a week of randomization.

Group Type: OTHER

Standard treatment

Intervention Type: OTHER

Participants randomized to standard treatment are recommended to follow updated guidelines for CVD prevention.

Interventions

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.

Intervention Type: OTHER

Standard treatment

Participants randomized to standard treatment are recommended to follow updated guidelines for CVD prevention.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

Per Løgstrup Poulsen

OTHER

Sponsor Role: lead

Responsible Party

Per Løgstrup Poulsen

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Per L Poulsen, Professor

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Aarhus, AUH, and Aarhus University

Axel Diederichsen, Professor

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Locations

Odense University Hospital

Odense, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Kristian L Funck, MD PhD

Role: CONTACT

klf@clin.au.dk

+4561331588

Per L Poulsen, Professor

Role: CONTACT

perpouls@rm.dk

Facility Contacts

Axel Diederichsen, phd

Role: primary

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

2022-500143-21-01

Identifier Type: -

Identifier Source: org_study_id