Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes — Steno1  

Heart Failure Clinical Trial

Official title: Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes

Status Not yet recruiting

Clinical Trial Summary

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.

Clinical Trial Description

Background: Individuals with type 1 diabetes (T1D) are at high risk for cardiovascular disease (CVD). Even with optimal glycemic control, the risk is doubled compared to healthy individuals. Treatment of type 2 diabetes (T2D) is based on multifactorial intervention (MFI). The development of new drug classes has had profound impact on treatment guidelines through a documented reduction in mortality and morbidity in individuals with T2D. MFI acknowledges the need for control and interventions directed towards several risk factors for CVD, and not focus merely on glucose levels. A fundamental change in risk management with a strong focus on MFIs to lower CVD risk in individuals with T1D and comorbidity of CVD, CKD, HF or obesity, has the potential to improve morbidity and survival in T1D.

Objective: The aim of the Steno 1 study is to test MFI in individuals with T1D at high risk of CVD with ambitious treatment targets. We hypothesize, that the MFI reduces major adverse cardiovascular endpoints (MACE) hospitalization for heart failure (HHF), kidney failure and mortality.

Design: This study uses a PROBE design (prospective, cluster-randomized, open, blinded endpoint evaluation), as it will not be possible to mask the MFI. The study is a superiority trial.

Patient population: High-risk individuals with T1D of >10 years duration (>40 years of age with presence of either CKD, CVD, HF, obesity or a >10% 5-year CVD risk determined by the Steno T1 Risk Engine). Participants are recruited from Steno Diabetes Centres or partner clinics.

Randomization: There will be formed three clusters (large patient pool, intermediate- and small). Within each cluster, participating centers will be randomised to either group A or group B. Group A will receive current guideline-recommended standard of care and group B will receive the multifactorial risk based intensive therapy. Participants are allocated to centers based on geography and not based on phenotype.

Intervention: For the intensively treated group, the MFI will be determined by the risk profile and risk markers of each individual and the participants will be allocated to Semaglutide, sotagliflozin, finerenone, ezetimibe and/ or PCSK9-inhibitors. The intervention will also comprise more ambitious treatment targets for blood pressure and lipid levels. In addition, all participants will take aspirin 75 mg OD.

Endpoints: The primary endpoint is to determine whether MFI 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). Secondary endpoints are to determine whether MFI is superior to standard care with respect to all-cause mortality, a composite endpoint of renal function (end-stage kidney disease (ESKD) (dialysis, renal death, transplantation) or >50% sustained decline in eGFR) compared to standard of care and to determine whether MFI including the use of SGLT2i and GLP1RA leads to an increased frequency of diabetic ketoacidosis compared to standard of care. ;

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Heart Failure
• Kidney Failure
• Renal Insufficiency
• Type 1 Diabetes

• NCT number: NCT06082063
• Study type: Interventional
• Source: Steno Diabetes Center Copenhagen
• Contact: Frederik Persson, MD, DMSc
• Phone: +4521623779
• Email: frederik.persson@regionh.dk
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 1, 2024
• Completion date: January 1, 2030