Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age40-90
SponsorSteno Diabetes Center Copenhagen
About this trial
A prospective, randomised, open-labelled, multi-center study. The aim of the Steno 1 study is to test multifactorial intervention in individuals with type 1 diabetes at high risk of CVD with ambitious treatment targets. We will include 2000 participants. Follow-up is 5 years.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Given written informed consent
Male or female patients ≥40 years old with type 1 diabetes (diagnosis before age 30 with insulin from onset or if diagnosis after 30 years of age insulin from onset and DKA or positive autoantibodies ( in accordance with local guidelines)) during >10 years.
Presence of chronic kidney disease (UACR >30 mg/g or eGFR < 60 ml/min/1.73 m2) OR history of ischemic heart disease (previous myocardial infarction, stroke or angina) OR history of heart failure OR obesity grade 2 and 3 (BMI>35 kg/m2) OR 10-year CVD risk >10% according to Steno Type 1 Risk Engine.
Fertile females must use highly efficient chemical, hormonal and mechanical contraceptives during the whole study and at least 2 months after cessation of study drug. The following contraceptive methods are approved: IUD or hormonal contraception that inhibits ovulation, i.e. pills, implantations, transdermal patches, vaginal ring or depot injection. Alternatively, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least 12 months prior to screening. Fertile participants will be pregnancy tested every six months with urine HCG.
Disqualifiers
Type 2 diabetes, MODY, secondary diabetes.
History of pancreatitis.
Body mass index < 18.5 kg/m2
Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods.
Trial design
Design model
Parallel
Treatments tested in this trial
Aspirin tablet
DrugAntiplatelet treatment: with aspirin 75mg OD is mandatory except for concomitant anticoagulant therapy or allergy. In case of allergy clopidogrel will be used.
Semaglutide
DrugGLP-1RA treatment: With semaglutide once weekly individually stepped highest tolerable dose according to standard guidelines aiming at 1 mg/week for persons with HbA1c \>53 mmol/mol or BMI\>25 kg/m2 and/or ischemic heart disease and/or stroke. For safety see below under benefits and risks. Investigators should pay attention to the need for adjustment in insulin dose after initiation of GLP-1RA treatment.
Sotagliflozin
DrugSGLT2i treatment with sotagliflozin 200 mg once daily for persons with UACR \>30 mg/g and eGFR \< 45 ml/min/1.73 m2 and for persons with a diagnosis of HF. For safety see below under benefits and risks. The limit of eGFR (\<45ml/min) for initiation of SGLT2i treatment is set to reduce risk of ketoacidosis. SGLT2i treatment should not be offered to participants on insulin pump therapy, to reduce risk of ketoacidosis. Investigators should pay attention to the need for adjustment in insulin dose after initiation of SGLT2i treatment.
Finerenone
DrugFinerenone: 10 mg once daily titrated to 20 mg as add-on in persons with persistent albuminuria (\>30 mg/g) despite RAS blockade.
Treatment groups
2,000 Participants
are divided into 2 treatment groupsGroup A: Multifactorial intervention groupActive comparator 4 interventions
Group B: Standard intervention groupNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
MACE + HHF
Calculate the incidence of cardiovascular events (MACE+HF) to determine whether a multifactorial intervention is superior to standard care with respect to MACE+HHF (composite of time to first non-fatal myocardial infarction, first non-fatal stroke, cardiovascular death or first hospitalization for heart failure).
Time frame
5 yearsSecondary outcomes
1
All-cause mortality
Calculate the incidence of all-cause mortality to determine whether a multifactorial intervention is superior to standard care with respect to all-cause mortality.
Time frame
5 years2
Renal function
Calculate the incidence of ESKD to determine whether a multifactorial intervention is superior to standard care with respect to renal function (end-stage kidney disease (ESKD) (dialysis, renal death, transplantation) or \>50% sustained decline in eGFR) compared to standard of care.
Time frame
5 years3
Diabetic ketoacidosis, safety
Calculate the incidence of DKA to determine whether a multifactorial intervention including the use of SGLT2i and GLP-1RA leads to a change in the frequency of diabetic ketoacidosis compared to standard care.
Time frame
5 yearsOther outcomes
1
Indivudual components of the primary endpoint
To determine whether a multifactorial intervention is superior to standard care with respect to the individual components of the primary endpoint.
Time frame
5 years2
Lower extremity amputations
Calculate the incidence of lower extremity amputations to determine whether a multifactorial intervention is superior to standard of care in reducing the total number of lower extremity amputations.
Time frame
5 years3
Progression of retinopathy
Calculate the incidence of progression to retinopathy to determine whether a multifactorial intervention is superior to standard of care in reducing progression of retinopathy.
Time frame
5 years4
Reduction in kidney function
Calculate the reduction in eGFR (ml/min/1.73m2) to determine whether a multifactorial intervention is superior to standard care with respect to sustained reduction in kidney function (\>30% decline in eGFR as well as \>40% decline in eGFR).
Time frame
5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Steno Diabetes Center Copenhagen
Lead sponsor
Aarhus University Hospital
Collaborator
Steno Diabetes Center Nordjylland
Collaborator
Steno Diabetes Center Odense
Collaborator
Slagelse Hospital
Collaborator
Nykøbing Falster County Hospital
Collaborator
Zealand University Hospital
Collaborator
Hillerod Hospital, Denmark
Collaborator
Rigshospitalet, Denmark
Collaborator
Hvidovre University Hospital
Collaborator
Regionshospitalet Viborg, Skive
Collaborator
Randers Regional Hospital
Collaborator
Herning Hospital
Collaborator
Esbjerg Hospital - University Hospital of Southern Denmark
Collaborator
Regionshospitalet Silkeborg
Collaborator
Bispebjerg Hospital
Collaborator
Regionshospitalet Horsens
Collaborator
Source ClinicalTrials.gov