Renal and Cardiovascular Effect of Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibition in Combination With Loop Diuretics in Diabetic Patients With Chronic Heart Failure
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- The Effect of Empagliflozin Versus Placebo on the Change in Urine Output.
研究概览
简要总结
The RECEDE-CHF trial is a single centre phase IV, randomised, double-blind, placebo-controlled, crossover trial conducted in NHS Tayside, Scotland comparing empagliflozin 25mg, to placebo in patients with Type 2 Diabetes and mild Chronic Heart Failure with left ventricular systolic dysfunction who are already on a loop diuretic. Renal physiological testing will be performed at two points on each arm to assess the effect of empagliflozin, on urinary volume, compared to placebo. The secondary outcomes are to assess the effect of empagliflozin in addition to loop diuretics on natriuresis, to assess the safety of add-on SGLT2 inhibitor therapy as measured by changes to serum creatinine and eGFR, to assess effects of empagliflozin on urinary protein/creatinine ratio, albumin/creatinine ratio and cystatin C when compared to placebo.
详细描述
Type 2 Diabetes (T2D) and Heart Failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium-glucose co-transporter 2 (SGLT2) inhibitors and their use in patients with HF. This is following publication of EMPA-REG OUTCOME trial that reported a 14% reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and >30% reductions in cardiovascular mortality, overall mortality and HF hospitalisations in patients randomised to the SGLT2 inhibitor, empagliflozin, when compared to placebo. Data on the effect of SGLT2 inhibitor use with diuretics is limited. We hypothesize that, in the diabetic CHF population, SGLT2 inhibition may augment the effects of loop diuretics.
Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. The investigational medicinal product will be administered, followed by an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose.
This proof of concept trial will aim to shed light on the mechanism of the cardiovascular and renal outcomes demonstrated in the recent EMPA-REG study by documenting the influence of the SGLT2 inhibitors when used in combination with a loop diuretic on diuresis and natriuresis when compared to placebo.
The RECEDE-CHF trial is funded by the British Heart Foundation (BHF grant number: 807998). NAM is a BHF funded clinical research fellow.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of NYHA Functional class II-III HF with prior echocardiographic evidence of LVSD.
- •On stable doses of furosemide, or alternative loop diuretic for at least one month.
- •Stable Type 2 Diabetes (HbA1c, in the last 3 months, of 6.5% ≤ and ≤10.0%)
- •eGFR ≥ 45 ml/min.
- •Have stable HF symptoms for at least three months prior to consent
- •On stable HF therapy for at least three months prior to consent
- •Have not been hospitalised for HF for at least three months prior to consent.
- •Women of childbearing potential must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.
排除标准
- •A diagnosis of chronic liver disease and/or liver enzymes that are twice the upper limit of normal
- •Systolic BP of <95mmHg at screening visit.
- •Participants on thiazide diuretics.
- •Participants receiving renal dialysis
- •Participants who have previously had an episode of diabetic ketoacidosis.
- •Participants with type 1 diabetes mellitus
- •Malignancy (receiving active treatment) or other life threatening disease.
- •Pregnant or lactating women
- •Participants with difficulty in micturition e.g. severe prostate enlargement
- •Allergy to any SGLT2 inhibitor or lactose or galactose intolerance
- •Past or current treatment with any SGLT2 inhibitor
- •Participants who have participated in any other clinical interventional trial of an investigational medicinal product within 30 days.
- •Participants who are unable to give informed consent
- •Any other reason considered by the physician to be inappropriate for inclusion.
研究组 & 干预措施
Empagliflozin/Placebo
Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks, minimum of a 2 week washout period, then 6 weeks placebo
干预措施: Empagliflozin 25mg (Drug)
Empagliflozin/Placebo
Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks, minimum of a 2 week washout period, then 6 weeks placebo
干预措施: Placebo oral capsule (Drug)
Empagliflozin/Placebo
Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks, minimum of a 2 week washout period, then 6 weeks placebo
干预措施: Frusemide (Drug)
Placebo/Empagliflozin
Placebo for 6 weeks, minimum of a 2 week washout period, followed by Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks
干预措施: Empagliflozin 25mg (Drug)
Placebo/Empagliflozin
Placebo for 6 weeks, minimum of a 2 week washout period, followed by Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks
干预措施: Placebo oral capsule (Drug)
Placebo/Empagliflozin
Placebo for 6 weeks, minimum of a 2 week washout period, followed by Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks
干预措施: Frusemide (Drug)
结局指标
主要结局
The Effect of Empagliflozin Versus Placebo on the Change in Urine Output.
时间窗: Change from baseline to 6 weeks
Change from urinary volume from baseline (mls).
次要结局
- The Effect of Empagliflozin Versus Placebo on the Change in Urinary Sodium Excretion.(Change from baseline to 6 weeks)
- Number of Participants With a Change in CKD Category as Dictated by the Glomerular Filtration Rate(From baseline to 6 weeks)
- The Effect of Empagliflozin Versus Placebo on the Change in Serum Creatinine.(Change from baseline to 6 weeks)
- The Effect of Empagliflozin Versus Placebo on the Change to Urinary Protein/Creatinine Ratio.(Change from baseline to 6 weeks)
- The Effect of Empagliflozin Versus Placebo on the Change to Urinary Albumin/Creatinine Ratio.(Change from baseline to 6 weeks)
- The Effect of Empagliflozin Versus Placebo on the Change to the Renal Biomarker, Cystatin C.(Change from baseline to 6 weeks)
研究者
Natalie Mordi
British Heart Foundation Clinical Research Fellow
University of Dundee