Screening and intervention for subclinical coronary artery disease in patients with type 2 diabetes: THE STENO INTEN-CT STUDY

The primary objective of the study is to evaluate the potential cardiovascular benefit of a treatment strategy based on a heart **CT scan** in patients with type 2 diabetes who have no known cardiovascular disease. This is clinically relevant as it aims to identify and manage subclinical coronary artery disease, potentially reducing the risk of future cardiovascular events in this high-risk population.

Secondary objectives include:

• Investigating the patient-reported outcomes of a screening and treatment program based on a heart CT scan.
• Calculating the cost-effectiveness of the proposed screening and treatment program.
• Evaluating and comparing the use of diagnostic tests and therapeutic interventions caused by the proposed screening program.
• Investigating if coronary CT angiography and echocardiography provide supplementary information on prognosis and treatment response beyond that provided by the proposed screening with CAC score.
• Evaluating novel biomarkers of subclinical cardiovascular damage that may add information on prognosis and treatment response beyond that provided by the proposed screening with CAC score.

The clinical trial involves participants diagnosed with **Type 2 diabetes** who do not have known cardiovascular disease. The study population includes both male and female subjects, with men aged between 55-69 years and women aged between 60-74 years. Participants are required to have a new or former diagnosis of Type 2 diabetes according to WHO criteria and must provide a signed declaration of consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the cardiovascular benefits of a treatment strategy based on a heart CT scan in patients with **type 2 diabetes** and no known cardiovascular disease. The trial employs a randomized, controlled, and open-label design, with a subset of patients receiving medications such as Forxiga and Ozempic, which are already approved for this patient population. The trial is categorized as a low-intervention study, with procedures posing minimal additional risk compared to standard clinical practice. The estimated duration of the trial is from September 2022 to September 2028, with participant involvement expected to last up to 96 weeks, depending on the treatment arm.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of type 2 diabetes, and consent. Following randomization, participants will attend regular follow-up visits to monitor treatment effects and safety. These visits will include assessments of cardiovascular endpoints, all-cause mortality, and renal function, as well as patient-reported outcomes using the EQ-5D questionnaire. The end-of-study visit will conclude the trial, with a comprehensive evaluation of the primary and secondary endpoints.

Participants may be withdrawn from the study early if they experience adverse events, withdraw consent, or if the investigator deems it necessary for safety reasons. The primary endpoint focuses on rates of a composite cardiovascular outcome, while secondary endpoints include separate cardiovascular events, quality-adjusted life years, and register-based rates of procedural codes and drug prescriptions. The trial aims to provide valuable insights into the management of cardiovascular risk in patients with type 2 diabetes, potentially influencing future treatment guidelines.

**Ozempic 1 mg solution for injection in pre-filled pen** is an experimental medication used in this clinical trial. It is a **solution for injection** administered via **subcutaneous injection**. The maximum daily dose is 0.14 mg, with a total maximum dose of 269 mg over a treatment period of up to 59 weeks. The active substance in this formulation is **semaglutide**. The product is manufactured by Novo Nordisk A/S and is not a pediatric formulation.

**Ozempic 0.25 mg solution for injection in pre-filled pen** is another experimental medication in the study. It is also a **solution for injection** administered via **subcutaneous injection**. The maximum daily dose is 0.14 mg, with a total maximum dose of 0.14 mg over a treatment period of up to 96 weeks. The active substance is **semaglutide**, and the product is manufactured by Novo Nordisk A/S.

**Nitrolingual Pumpspray 400 micrograms per metered dose, sublingual spray** is used as a non-experimental treatment in the trial. It is a **sublingual spray** containing **glyceryl trinitrate** as the active substance. The maximum daily dose is 3 metered doses, with a total maximum dose of 3 doses per day. The product is manufactured by G. Pohl-Boskamp GmbH & Co. KG.

**Ivabradin Medical Valley 5 mg film-coated tablets** are used as a non-experimental treatment. These are **film-coated tablets** administered **orally**. The active substance is **ivabradine**, with a maximum daily dose of 15 mg and a total maximum dose of 15 mg per day. The product is manufactured by Medical Valley Invest AB.

**Forxiga 10 mg film-coated tablets** are another non-experimental treatment in the study. These **film-coated tablets** are administered **orally**. The active substance is **dapagliflozin**, with a maximum daily dose of 10 mg and a total maximum dose of 16800 mg over a treatment period of up to 60 weeks. The product is manufactured by AstraZeneca AB.

**Iomeron 350 mg I/ml solution for injection** is used as a non-experimental treatment. It is a **solution for injection** administered via **IV infusion**. The active substance is **iomeprol**, with a maximum daily dose of 250 ml and a total maximum dose of 250 ml per day. The product is manufactured by Bracco Imaging S.p.A.

**Seloken 1 mg/ml solution for injection** is another non-experimental treatment. It is a **solution for injection** administered via **intravenous administration**. The active substance is **metoprolol tartrate**, with a maximum daily dose of 15 mg and a total maximum dose of 15 mg per day. The product is manufactured by AstraZeneca AB.

**Atenolol Orifarm 50 mg tablets** are used as a non-experimental treatment. These are **tablets** administered **orally**. The active substance is **atenolol**, with a maximum daily dose of 100 mg and a total maximum dose of 100 mg per day. The product is manufactured by Orifarm Generics A/S.

**Ozempic 0.5 mg solution for injection in pre-filled pen** is an experimental medication in the study. It is a **solution for injection** administered via **subcutaneous injection**. The maximum daily dose is 0.14 mg, with a total maximum dose of 0.14 mg over a treatment period of up to 96 weeks. The active substance is **semaglutide**, and the product is manufactured by Novo Nordisk A/S.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the rate of a composite cardiovascular endpoint, which includes cardiovascular death, non-fatal myocardial infarction, hospitalization for heart failure, non-fatal stroke, and revascularization of peripheral artery disease. Secondary endpoints encompass separate cardiovascular endpoints, all-cause mortality, and **renal failure**. Additionally, patient-reported outcomes will be evaluated using the EQ-5D questionnaire, and quality-adjusted life years (QALY) will be calculated using data from the EQ-5D questionnaire along with Danish preference weights of the normal population. Register-based rates of procedural codes for tests related to atherosclerosis or ischemia of the heart, brain, or peripheral circulation, as well as rates of prescription of drugs used in cardiovascular disease prophylaxis, will also be considered.