Effects of Sodium-Glucose Cotransporter 2 Inhibition on the Mechanisms of Cardiac Damage in the Diabetic Patient With Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Functional Main Objective: Impact of iSGLT2 on LV diastolic properties in terms of the change in LV stiffness constant (S+) at the peak of exercise.
研究概览
简要总结
The main aim of this study is to identify the underlying mechanisms of Sodium-glucose co-transporter-2 (SGLT2) inhibitors which are associated to better outcomes in patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction.
详细描述
Double design study including a clinical trial and a nested case-control study.
A) Experimental study (clinical trial): Phase IV, prospective, randomized, double-blind placebo-controlled with 12 months follow-up. Inclusion criteria are: 1) diagnosis of DM2, 2) HF with preserved EF with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction. 3) Stable clinical situation at inclusion. 4) Clinical indication of cardiac catheterization.
Patients will be randomized 1:1 to received Dapagliflozin 10 mg/day or placebo. The main objective is to compare the impact of the drug on LV diastolic properties at the peak of effort and in levels of plasma deposit and cross-linking biomarkers of type I collagen between the two treatment groups at baseline and after 12 months.
52 patients will be recruited.
B) Descriptive study: Nested case-control study, considering patients from the experimental study as cases and 10 additional patients with HF with preserved EF but no type 2 DM as controls. The main aim will be compare the histological, molecular, biochemical and biomechanical features of the HFpEF patients with and without DM2.
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
- •Diagnosis of DM2 based on the established criteria: HbA1c ≥ 6.5% (48 mmol / mol) and fasting plasma glucose ≥ 7.0 mmol / L (≥126 mg / dL) or 2-h after overload ≥ 11.1 mmol / L ( ≥ 200 mg / dL).
- •LVEF ≥ 50%.
- •Diagnosis of ICFEP according to clinical criteria, with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction according to the echocardiographic criteria.
- •Stable clinical situation (> 1 month after hospitalization due to IC decompensation).
- •Clinical indication of cardiac catheterization.
- •Signature of informed consent.
排除标准
- •Previous treatment with iSGLT
- •Significant coronary disease.
- •Aortic or mitral valve disease ≥ moderate (grades 3 or 4/4 for valve regurgitations)
- •Contraindications for dapagliflozin treatment according to the data sheet (hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption, moderate-severe renal failure -CrCl <60 ml / min or eGFR <60 ml / min / 1 , 73 m2-, severe hepatic insufficiency).
- •The inclusion/exclusion criteria for Descriptive Study will be the same as previously described without the diagnosis of DM2.
研究组 & 干预措施
Clinical Trial: Experimental Arm
Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Dapagliflozin (Forxiga) 10 mg, one capsule per day orally.
干预措施: Dapagliflozin 10 MG [Farxiga] (Drug)
Clinical Trial: Placebo Arm
Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Placebo in a similar pattern.
干预措施: Placebo (Drug)
结局指标
主要结局
Functional Main Objective: Impact of iSGLT2 on LV diastolic properties in terms of the change in LV stiffness constant (S+) at the peak of exercise.
时间窗: Baseline vs 12 months
Intrinsic diastolic properties will be analyzed by dynamic pressure-volume loop catheterization.
Main Structural Objective: Changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL)
时间窗: Baseline vs 12 months
We will measure the changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL), a validated biomarker of collagen type I deposition
次要结局
- Correlation of myocardial remodeling patterns with the intrinsic diastolic properties of chamber VI with systolic function.(Baseline vs 12 months)
- Changes in N-terminal pro brain natriuretic peptide (pg/mL)(Baseline vs 12 months)
- Changes in high sensitivity troponin T (pg/mL)(Baseline vs 12 months)
- Changes in LV stiffness constants (S+ and S-).(Baseline vs 12 months)
- Changes in the slope, Emax, of the end-systolic pressure-volume relationship(Baseline vs 12 months)
- Relative contribution of the intrinsic diastolic properties of the LV and the flow patterns on filling pressures and their modulation under treatment with iSGLT2.(Baseline vs 12 months)
- Impact of iSGLT2 on myocardial remodeling.(Baseline vs 12 months)
- Changes in serum levels of collagen type I C-terminal telopeptide to matrix metalloproteinase ratio (CITP:MMP-1)(Baseline vs 12 months)