Insulin Treatment in Diabetic Older People With Heart Failure.

NCT03665350 | Terminated Phase 2 DMC

• 2 other identifiers: IRFMN-74682018-001057-26
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Heart Failure; Diabetes Mellitus, Type 2

Keywords

Heart Failure; Type 2 diabetes mellitus; Insulin; Older adults

Outcome Measures

Primary Outcomes (1)

• 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).

  baseline to 12 months.

Secondary Outcomes (13)

• Number of patients with episodes of hypoglycemia.

  baseline, 1, 6, 12 months.

• Change in body weight.

  baseline, 1, 6, 12 months.

• Change in plasma concentration of a natriuretic peptide

  baseline, 1, 6, 12 months.

• Changes in urinary albumin excretion

  baseline, 1, 6, 12 months.

• Change in New York Heart Association (NYHA) class

  baseline, 1, 6, 12 months.

Study Arms (2)

non insulin

NO INTERVENTION

standard care + antidiabetic therapy non insulin

Insulin

EXPERIMENTAL

standard care including insulin

Drug: Insulin

Interventions

Insulin DRUG

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.

Insulin

Eligibility Criteria

• Age: 70 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 \[ULN\]);
• levels of hemoglobin \<10 g/dl;
• HbA1c ≤5% or ≥11%;
• unstable diabetes: type of diabetes presentation in patients with an anamnesis of frequent episodes of hypoglycemia, hyperglycemic hyperosmolar state, ketoacidosis or lactic acidosis;
• planned CV surgery or angioplasty in 3 months;
• any non-cardiac disease that shortens life expectancy to\<1 year (e.g.most cancers);
• inability to comply with study protocol;
• participation to another interventional clinical study.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (3)

Ospedale Bolognini di Seriate

Seriate, BG, 24068, Italy

Location

Ospedale Treviglio

Treviglio, BG, 24047, Italy

Location

Ospedale di Passirana

Passirana, MI, 20017, Italy

Location

Related Publications (9)

• American Diabetes Association. 11. Older Adults: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S119-S125. doi: 10.2337/dc18-S011.

  PMID: 29222382 BACKGROUND

• Aspromonte N, Gulizia MM, Di Lenarda A, Mortara A, Battistoni I, De Maria R, Gabriele M, Iacoviello M, Navazio A, Pini D, Di Tano G, Marini M, Ricci RP, Alunni G, Radini D, Metra M, Romeo F. ANMCO/SIC Consensus Document: cardiology networks for outpatient heart failure care. Eur Heart J Suppl. 2017 May;19(Suppl D):D89-D101. doi: 10.1093/eurheartj/sux009. Epub 2017 May 2.

  PMID: 28751837 BACKGROUND

• Bozkurt B, Aguilar D, Deswal A, Dunbar SB, Francis GS, Horwich T, Jessup M, Kosiborod M, Pritchett AM, Ramasubbu K, Rosendorff C, Yancy C; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; Council on Hypertension; and Council on Quality and Outcomes Research. Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016 Dec 6;134(23):e535-e578. doi: 10.1161/CIR.0000000000000450. Epub 2016 Oct 31. No abstract available.

  PMID: 27799274 BACKGROUND

• Cosmi F, Shen L, Magnoli M, Abraham WT, Anand IS, Cleland JG, Cohn JN, Cosmi D, De Berardis G, Dickstein K, Franzosi MG, Gullestad L, Jhund PS, Kjekshus J, Kober L, Lepore V, Lucisano G, Maggioni AP, Masson S, McMurray JJV, Nicolucci A, Petrarolo V, Robusto F, Staszewsky L, Tavazzi L, Teli R, Tognoni G, Wikstrand J, Latini R. Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. Eur J Heart Fail. 2018 May;20(5):888-895. doi: 10.1002/ejhf.1146. Epub 2018 Feb 28.

  PMID: 29488676 BACKGROUND

• DeVries JH. Glucose variability: where it is important and how to measure it. Diabetes. 2013 May;62(5):1405-8. doi: 10.2337/db12-1610.

  PMID: 23613566 BACKGROUND

• DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest. 1975 Apr;55(4):845-55. doi: 10.1172/JCI107996.

  PMID: 1120786 BACKGROUND

• Giorda CB, Rossi MC, Ozzello O, Gentile S, Aglialoro A, Chiambretti A, Baccetti F, Gentile FM, Romeo F, Lucisano G, Nicolucci A; HYPOS-1 Study Group of AMD. Healthcare resource use, direct and indirect costs of hypoglycemia in type 1 and type 2 diabetes, and nationwide projections. Results of the HYPOS-1 study. Nutr Metab Cardiovasc Dis. 2017 Mar;27(3):209-216. doi: 10.1016/j.numecd.2016.10.005. Epub 2016 Nov 18.

  PMID: 28017523 BACKGROUND

• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-e161. doi: 10.1161/CIR.0000000000000509. Epub 2017 Apr 28. No abstract available.

  PMID: 28455343 BACKGROUND

• ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.

  PMID: 22686416 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Insulin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Lidia Staszewsky, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Insulin-HF is a randomized, open-label, controlled, multicenter (PROBE design, prospective Randomized Open Trial with Blinded Evaluation of Outcomes), and central adjudication of adverse events. All study events, clinical and laboratory, will be independently validated by an Event Committee
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The primary endpoint, glucose variability, will be computed from 3 daily glucose profiles performed before the baseline, 1, 6, 12 mo follow-up and at end study visit and calculated as the average of the three daily standard deviations. Blood glucose values will be reported by the patient in an ad hoc form and the responsible physician will input this data in the e-CRF. An intensive ambulatory self-monitoring of weekly body weight and possible changes in diuretic treatment is required. At 1, 6, 12 mo of follow up and/or at end of study visit: 1. patients will be examined, 2. the information about clinical events will be collected. 3. natriuretic peptide plasma concentration, HbA1c and urinary albumin excretion will be measured Echocardiographic evaluation will be done at baseline, 1 and 12 mo after randomization. Central randomization in a 1:1 ratio will be performed by a web-based system.

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: September 11, 2018
• Study Start: November 8, 2018
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: November 18, 2019

Record last verified: 2019-11

Locations

IT (3)