A Phase 2 interventional study of Insulin in Heart Failure and Diabetes Mellitus, Type 2, sponsored by Mario Negri Institute for Pharmacological Research. Terminated at 3 sites in Italy. Open to participants aged 70 Years to 100 Years. Per ClinicalTrials.gov, last updated 2019-11-18.
Sponsored by Mario Negri Institute for Pharmacological Research · Phase 2, Interventional, and Treatment
Cardiac failure (HF) and type 2 diabetes mellitus (T2DM) are two clinical conditions with a significant impact on public health worldwide. In the elderly population the prevalence of T2DM is constantly increasing as well as its incidence in all Western countries including Italy. The combination of HF and T2DM is frequent and leads to an increased risk of death and of non-fatal adverse cardiovascular (CV) events which justifies the frailty of this population. Although diabetic patients (pts) with HF respond to recommended treatments for HF, the effective and safe control of blood glucose levels is still an outstanding clinical problem, since glucose lowering drugs may increase the risk of CV adverse events. Insulin, used in about 30% of diabetic patients with HF, causes adverse effects such as fluid and sodium retention and unwanted effects of hypoglycemia. Even if insulin remains a milestone in glucose lowering therapy of T2DM, its risk/benefit ratio is still controversial, more so when given to old patients with HF. The issue has gained relevance since new antidiabetic agents, as the sodium glucose co-transporter 2 (SGLT- 2) inhibitors and glucagon-like peptide (GLP-1) analogues, with a safer CV profile have been made available. While the transferability of the CV benefits attributed to the new drugs needs to be assessed in clinical practice, the present study explore the benefit/risk profile of insulin in HF.
Objectives: to assess comparatively in patients with heart failure and T2DM the benefit/risk profile over 1-year follow-up of two antidiabetic strategies, standard care with vs without insulin in terms of humoral and clinical endpoints including body weight change, all-cause mortality and burden of care components (hospitalizations for CV events and episodes of severe hypoglycemia).
The project will consist in a controlled, randomized, open-label (PROBE design) multicenter, pilot study. Central randomization stratified by center, performed online, will allow a comparison of two groups of patients one receiving standard care including insulin, the other standard care without insulin. Patients considered not eligible for randomization will be included in a registry.
The first objective of this exploratory randomized study is to assess in patients with heart failure and T2DM if a standard anti-diabetic strategy which includes insulin has a different safety and efficacy profile than one without insulin. The number of patients to be included in this exploratory pilot study will be insufficient to prove or disprove a statistically significant beneficial effect of the two antidiabetic strategies on clinical events. Special care will be paid to the biologic consistency of the different endpoints, primary and secondary, even if none of them will individually yield statistically significant differences.
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's enrollment of 10 is below the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Mario Negri Institute for Pharmacological Research is the lead sponsor of 159 studies on the registry; 36 are open to participants now.
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Exclusion Criteria:
standard care + antidiabetic therapy non insulin
standard care including insulin
Drug: Insulin
Insulin as well as oral anti-diabetic drugs will be prescribed by the responsible physician and/or the diabetologist from each participating site, in conformity with the current guidelines, and the therapeutic target chosen according to patient characteristics. The choice of anti-diabetic medications should be guided by medical needs of each patient and taking into consideration their general safety profile.
Change in blood glucose variability
Mean change from baseline to 12 months in glucose variability. Glucose variability is estimated as standard deviation (SD) of serial glycemic values, and is based on 3 daily glucose profiles (each with at least 5 self-measurements of blood glucose).
Time frame: baseline to 12 months.
Number of patients with episodes of hypoglycemia.
Hypoglycemic episodes: an event accompanied or not accompanied by typical symptoms but with a measured plasma glucose concentration ≤70 mg/dl (3.9 mmol/l).
Time frame: baseline, 1, 6, 12 months.
Change in body weight.
Weight will be measured in Kg. An increase in body weight ≥2 kg gain in one week will be considered a marker of fluid congestion.
Time frame: baseline, 1, 6, 12 months.
Change in plasma concentration of a natriuretic peptide
BNP or NT-proBNP concentrations will be measured as ng/L of plasma.
Time frame: baseline, 1, 6, 12 months.
Changes in urinary albumin excretion
Urinary albumin concentration will be expressed as the urinary albumin-to-creatinine ratio (UACR), measured in milligrams per grams of creatinine, with a limit of detection of 1.5 mg/g.
Time frame: baseline, 1, 6, 12 months.
Change in New York Heart Association (NYHA) class
Any change in NYHA class. The New York Heart Association (NYHA) Functional Classification places patients in one of four categories (I through IV) based on heart failure symptoms and functional limitations. Higher NYHA classes indicate a greater heart failure severity and poorer outcome."
Time frame: baseline, 1, 6, 12 months.
All-cause hospitalizations
Number of patients admitted to hospital for any cause.
Time frame: baseline to 12 months
Hospitalizations for worsening of HF.
Number of patients admitted to hospital for worsening of HF.
Time frame: baseline to 12 months
All-cause mortality
Number of patients who died for cardiovascular and non-cardiovascular causes.
Time frame: baseline to 12 months
Number of patients with episodes of ketoacidosis as evaluation of safety.
Ketoacidosis is defined as the presence of at least two of the following factors: a) elevated plasma glucose (\>250 mg/dL), b) ketones in serum or urine and c) acidosis (serum bicarbonate \<18 mEq/L and/or pH \<7.30).
Time frame: baseline to 12 months
Number of patients with episodes of lactic acidosis as evaluation of safety.
Lactic acidosis is characterized by persistently increased blood lactate levels (usually \>5 mmol/L) in association with metabolic acidosis.
Time frame: baseline to 12 months
Changes in left ventricular ejection fraction (LVEF).
LVEF will be calculated from left ventricular volume in diastole and systole estimated by echocardiography. LVEF will be measured as percentage. A decrease in LVEF will be taken as a marker of worsening of cardiac function.
Time frame: baseline, 1, 6, 12 months.
Changes in E/e'.
E/e' ratio will be calculated from echo-Doppler recordings. As a ratio it will not have a unit of measure.
Time frame: baseline, 1, 6, 12 months.
Changes in Hemoglobin A1c (HbA1c).
HbA1c will be measured as percentage of total hemoglobin concentration.
Time frame: baseline, 1, 6, 12 months.
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This study is terminated, as verified in Nov 2019. You cannot join it, but the record below documents what was studied.
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Mario Negri Institute for Pharmacological Research