Research Into the Effect of SGLT2 Inhibition on Left Ventricular Remodeling in Patients With Heart Failure and Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Change in LV end systolic volume (absolute value and indexed for BSA) or LV end diastolic volume (absolute value and indexed for BSA)
研究概览
简要总结
Patients with diabetes are at increased risk of developing heart failure (HF) which can lead to increased shortness of breath, reduced ability to exercise and in some cases premature death as the heart becomes less efficient at pumping blood around the body. However the treatment options for such patients remain limited.
This study will test the safety and benefits of using a new class of drug, the SGLT2 Inhibitor (Dapagliflozin), in treating HF and diabetes.
Participants will have a Magnetic Resonance Imaging (MRI) scan of the heart, to measure the efficiency and the extent of thickening of the heart muscle before they start on treatment of dapagliflozin, or placebo for one year. They will also do exercise testing on an exercise bike (if capable) and a walking test plus fill in some questionnaires on how their heart failure affects their quality of life. Participants will then continue as normal with currently prescribed medication for their diabetes and heart failure. After a year the tests will be repeated to determine if patients receiving Dapagliflozin benefited more than those who weren't on the drug.
This study is funded by the European Foundation for the Study of Diabetes (EFSD)
详细描述
Men and women with diabetes have a 2-5-fold increased risk of heart failure (HF). The prevalence and incidence of HF is increasing in diabetes and mortality rates remain alarmingly high. This highlights the need for novel therapies in diabetes that will reduce HF risk and /or delay disease progression.
Drug options are currently limited as some diabetic therapies such as thiazolidinediones are contra-indicated in HF. SGLT2 inhibitors, the newest class of anti-diabetic drugs, are an exciting new approach to diabetes management that may have additional beneficial effects in diabetes and HF. SGLT2 inhibitors may have beneficial effects on adverse left ventricular (LV) remodelling that occurs in patients with diabetes and heart failure by reducing the load on the heart through its diuretic and blood pressure lowering actions.
Exercise intolerance is a cardinal symptom of patients with HF and improving insulin sensitivity has been shown to improve exercise capacity. SGLT2 inhibition has been shown to improve insulin sensitivity and to reduce weight and therefore has the potential to improve exercise capacity in HF.
This study will assess the potential beneficial effects of the oral SGLT2 inhibitor, dapagliflozin, on LV remodelling and exercise capacity in patients with diabetes and HF. The findings of this study may help to establish the utility of SGLT2 inhibitors in diabetic patients with HF and provide important clinical data on the impact of SGLT2 inhibition on LV remodelling.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •were previously diagnosed with Type 2 Diabetes
- •are diagnosed with NYHA functional class I-III HF with prior echocardiographic evidence of Left Ventricular Systolic Dysfunction (LVSD) (At least mild LV systolic dysfunction on sonographer assessment or ejection fraction at 45% or less)
- •on furosemide 80mg daily or less, or equivalent loop diuretic
- •have stable HF symptoms for at least three months prior to consent
- •on stable therapy for HF for at least three months prior to consent
- •have not been hospitalised for HF for at least three months prior to consent
排除标准
- •severe hepatic disease
- •renal disease defined as Chronic Kidney Disease (CKD) class 3b or worse (i.e. estimated glomerular filtration rate (eGFR) / creatinine clearance CrCl <45ml/min)
- •systolic BP <95mmHg at screening visit
- •screening HbA1c <6.0%
- •unable to walk to perform cardio pulmonary exercise testing or 6MWT
- •malignancy (receiving active treatment) or other life threatening diseases
- •pregnant or lactating women
- •any contraindication to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
- •patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days
- •patients who are unable to give informed consent
- •any other reason considered by a study physician to be inappropriate for inclusion.
研究组 & 干预措施
Treatment
Dapagliflozin 10mg once daily
干预措施: Dapagliflozin (Drug)
Control
Capsules containing microcrystalline cellulose Ph Eur overencapsulated in a hard gelatine capsule shell to match the active comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Change in LV end systolic volume (absolute value and indexed for BSA) or LV end diastolic volume (absolute value and indexed for BSA)
时间窗: 1 year
Cardiac MRI will be performed to determine the change in end systolic and diastolic volumes between both groups of patients
次要结局
- Objective functional capacity (6 Minute Walk Test (6MWT)(1 year)
- Cardiac and inflammatory biomarkers(1 year)
- The safety of dapagliflozin use in diabetic, heart failure patients with regard to worsening HF, hospitalization and death will be evaluated(1 year)
- Fluid status (Bioelectrical Impedence Analysis (BIA)(1 year)
- Quality of life (Minnesota Living with Heart Failure and SF-36 questionnaire)(1 year)
- Quantify amount of natriuresis(1 year)
- Change in LV mass, LV ejection fraction, RV end diastolic volume, RV end systolic volume, RV ejection fraction, atrial dimensions and volumes, and LV remodelling index (LV mass / LVEDV)(1 year)
- Diuretic requirement (total diuretic requirement to maintain euvolemia)(1 year)
- Change in degree of microalbuminuria(1 year)
- Exercise capacity (Cardio-pulmonary Exercise Testing (CPET)(1 year)
研究者
Jagdeep Singh Surmukh Singh
Dr
University of Dundee