{
  "abstract": "Introduction Cardiovascular disease (CVD) risk remains high but unevenly distributed in patients with type 2 diabetes mellitus (T2DM). Current risk stratification strategies are far from optimal, leading to both undertreatment and overtreatment of patients. The STENO INTEN-CT trial aims to evaluate a strategy of improved CVD risk management by using cardiac CT (coronary artery calcification (CAC)) for stratification and tailoring of multifactorial cardiovascular treatment based on CAC score. We hypothesise that (1) intensified medical treatment will lower CVD event rates in high-risk patients (CAC≥100), and (2) less intensive multifactorial treatment is safe in very low-risk patients (CAC=0).Methods and analysis The Steno INTEN-CT trial is an investigator-initiated, pragmatic, open-label, event-driven randomised controlled trial including patients with T2DM without known CVD. All participants (expected n=7300) will be invited for a non-contrast coronary CT scan. After the scan, participants will be randomised to either standard treatment (blinded for CAC results) or CAC-based treatment. Participants in CAC-based treatment and their general practitioner (GP) will receive information on CAC and a recommendation of multifactorial treatment. High-risk participants in the interventional arm will be invited for one or more initial study visits to intensify treatment with a combination of sodium glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, high-dose lipid-lowering, antihypertensive and antithrombotic treatment. Very low-risk patients in the interventional arm will be recommended less intensive treatment targets. After initial study-related activities, all participants will continue to be taken care of by their GP guided by specific treatment recommendations. The primary outcome in the primary hierarchical analysis (the rate of the combined CVD endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for heart failure) will be monitored through national health registries. The trial is event-driven, but a median follow-up of 5 years is expected. Key secondary outcomes include patient-reported outcomes, quality-adjusted life years and healthcare costs.Ethics and dissemination The protocol V.1.9 is approved by the Research Ethics Committee and the Danish Medicines Agency and the Danish Data Protection Agency. The results of the study—positive, negative or neutral—will be published in peer-reviewed journals and through www.clinicaltrials.org.Trial registration number NCT05700877.",
  "authors": [
    {
      "affiliations": [
        "Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark"
      ],
      "name": "Kristian Løkke Funck"
    },
    {
      "affiliations": [
        "Department of Cardiology, Odense University Hospital, Odense, Denmark"
      ],
      "name": "Britt Borregaard"
    },
    {
      "affiliations": [
        "Cardiovascular Center of Excellence Southern DK, Svendborg Sygehus, Svendborg, Syddanmark, Denmark",
        "Steno Diabetes Center Odense, Odense University Hospital, Odense, Region Syddanmark, Denmark"
      ],
      "name": "Kenneth Egstrup"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark"
      ],
      "name": "Eskild Klausen Fredslund"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark"
      ],
      "name": "Tine Willum Hansen"
    },
    {
      "affiliations": [
        "Research Unit of General Practice, Department of Public Health, Aarhus Universitet, Aarhus, Denmark"
      ],
      "name": "Per Kallestrup"
    },
    {
      "affiliations": [
        "Department of Internal Medicine and Steno Diabetes Center Zealand, Holbaek Hospital, Holbæk, Region Zealand, Denmark",
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark"
      ],
      "name": "Michael Hecht Olsen"
    },
    {
      "affiliations": [
        "Department of Public Health, Copenhagen University Section of General Practice, Copenhagen, Denmark"
      ],
      "name": "Susanne Reventlow"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark"
      ],
      "name": "Peter Rossing"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark"
      ],
      "name": "Annelli Sandbæk"
    },
    {
      "affiliations": [
        "Research Unit of General Practice, University of Southern Denmark, Odense, Region Syddanmark, Denmark"
      ],
      "name": "Jens Søndergaard"
    },
    {
      "affiliations": [
        "Center for General Practice, Aalborg University, Aalborg, North Denmark Region, Denmark"
      ],
      "name": "Janus Laust Thomsen"
    },
    {
      "affiliations": [
        "Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, North Denmark Region, Denmark",
        "Aalborg Universitet, Aalborg, North Denmark Region, Denmark"
      ],
      "name": "Peter Vestergaard"
    },
    {
      "affiliations": [
        "Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark"
      ],
      "name": "Per Løgstrup Poulsen"
    },
    {
      "affiliations": [
        "Department of Cardiology, Odense University Hospital, Odense, Denmark",
        "Steno Diabetes Center Odense, Odense University Hospital, Odense, Region Syddanmark, Denmark"
      ],
      "name": "Axel Diederichsen"
    }
  ],
  "title": "Study protocol for the investigator-initiated Danish pragmatic randomised STENO INTEN-CT trial: does screening and intervention for subclinical coronary artery disease in type 2 diabetes reduce cardiovascular events?",
  "uid": "1e1552a7-770b-5518-b946-b28ddee399e9"
}