Insulin Treatment in Diabetic Older People With Heart Failure. (Insulin-HF)

November 15, 2019 updated by: Mario Negri Institute for Pharmacological Research

Management of the Patient With Heart Failure and Diabetes: May Insulin be a Problem? A Pilot Randomized Clinical Study (Insulin-HF)

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • BG
      • Seriate, BG, Italy, 24068
        • Ospedale Bolognini di Seriate
      • Treviglio, BG, Italy, 24047
        • Ospedale Treviglio
    • MI
      • Passirana, MI, Italy, 20017
        • Ospedale di Passirana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years to 100 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. men and women aged ≥70 years;
  2. at discharge after admission to hospital for worsening of HF or ambulatory patients with chronic HF;
  3. New York Heart Association (NYHA) class II or III
  4. with any level of left ventricular ejection fraction;
  5. plasma natriuretic peptide (BNP) ≥200 pg/mL or N-terminal pro-BNP ≥900 pg/mL (NT pro-BNP)
  6. prior history or newly diagnosed T2DM;
  7. candidate by the responsible physician to insulin therapy;
  8. signed informed consent.

Exclusion Criteria:

  1. significant renal insufficiency (GFR <30 mL/min/1.73 m2) or severe liver disease (liver function test abnormalities (alanine or aspartate aminotransferase ≥ 3 × upper limit of normal [ULN]);
  2. levels of hemoglobin <10 g/dl;
  3. HbA1c ≤5% or ≥11%;
  4. unstable diabetes: type of diabetes presentation in patients with an anamnesis of frequent episodes of hypoglycemia, hyperglycemic hyperosmolar state, ketoacidosis or lactic acidosis;
  5. planned CV surgery or angioplasty in 3 months;
  6. any non-cardiac disease that shortens life expectancy to<1 year (e.g.most cancers);
  7. inability to comply with study protocol;
  8. participation to another interventional clinical study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: non insulin
standard care + antidiabetic therapy non insulin
Experimental: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in blood glucose variability
Time Frame: baseline to 12 months.
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).
baseline to 12 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with episodes of hypoglycemia.
Time Frame: baseline, 1, 6, 12 months.
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).
baseline, 1, 6, 12 months.
Change in body weight.
Time Frame: baseline, 1, 6, 12 months.
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.
baseline, 1, 6, 12 months.
Change in plasma concentration of a natriuretic peptide
Time Frame: baseline, 1, 6, 12 months.
BNP or NT-proBNP concentrations will be measured as ng/L of plasma.
baseline, 1, 6, 12 months.
Changes in urinary albumin excretion
Time Frame: baseline, 1, 6, 12 months.
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.
baseline, 1, 6, 12 months.
Change in New York Heart Association (NYHA) class
Time Frame: baseline, 1, 6, 12 months.
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."
baseline, 1, 6, 12 months.
All-cause hospitalizations
Time Frame: baseline to 12 months
Number of patients admitted to hospital for any cause.
baseline to 12 months
Hospitalizations for worsening of HF.
Time Frame: baseline to 12 months
Number of patients admitted to hospital for worsening of HF.
baseline to 12 months
All-cause mortality
Time Frame: baseline to 12 months
Number of patients who died for cardiovascular and non-cardiovascular causes.
baseline to 12 months
Number of patients with episodes of ketoacidosis as evaluation of safety.
Time Frame: baseline to 12 months
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).
baseline to 12 months
Number of patients with episodes of lactic acidosis as evaluation of safety.
Time Frame: baseline to 12 months
Lactic acidosis is characterized by persistently increased blood lactate levels (usually >5 mmol/L) in association with metabolic acidosis.
baseline to 12 months
Changes in left ventricular ejection fraction (LVEF).
Time Frame: baseline, 1, 6, 12 months.
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.
baseline, 1, 6, 12 months.
Changes in E/e'.
Time Frame: baseline, 1, 6, 12 months.
E/e' ratio will be calculated from echo-Doppler recordings. As a ratio it will not have a unit of measure.
baseline, 1, 6, 12 months.
Changes in Hemoglobin A1c (HbA1c).
Time Frame: baseline, 1, 6, 12 months.
HbA1c will be measured as percentage of total hemoglobin concentration.
baseline, 1, 6, 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mario Negri Institute for Pharmacological Research

Investigators

  • Principal Investigator: Lidia Staszewsky, MD, Istituto Di Ricerche Farmacologiche Mario Negri

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 8, 2018

Primary Completion (Actual)

September 18, 2019

Study Completion (Actual)

September 18, 2019

Study Registration Dates

First Submitted

July 26, 2018

First Submitted That Met QC Criteria

September 7, 2018

First Posted (Actual)

September 11, 2018

Study Record Updates

Last Update Posted (Actual)

November 18, 2019

Last Update Submitted That Met QC Criteria

November 15, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRFMN-7468
  • 2018-001057-26 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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