Management of the Patient With Heart Failure and Diabetes: May Insulin be a Problem? A Pilot Randomized Clinical Study (Insulin-HF)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Change in blood glucose variability
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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
入排标准
- 年龄范围
- 70 Years 至 100 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Insulin
standard care including insulin
干预措施: Insulin (Drug)
结局指标
主要结局
Change in blood glucose variability
时间窗: 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).
次要结局
- Changes in E/e'.(baseline, 1, 6, 12 months.)
- Changes in Hemoglobin A1c (HbA1c).(baseline, 1, 6, 12 months.)
- Number of patients with episodes of hypoglycemia.(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.)
- Hospitalizations for worsening of HF.(baseline to 12 months)
- All-cause mortality(baseline to 12 months)
- Number of patients with episodes of ketoacidosis as evaluation of safety.(baseline to 12 months)
- Number of patients with episodes of lactic acidosis as evaluation of safety.(baseline to 12 months)
- Changes in left ventricular ejection fraction (LVEF).(baseline, 1, 6, 12 months.)
- Change in body weight.(baseline, 1, 6, 12 months.)
- Change in New York Heart Association (NYHA) class(baseline, 1, 6, 12 months.)
- All-cause hospitalizations(baseline to 12 months)