Canagliflozin in Advanced Renal Disease With MRI Endpoints
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Change in left ventricular mass to volume ratio (LVMV) from baseline to 12 months, as assessed by cardiac MRI compared with placebo
研究概览
简要总结
This is a phase II, proof of concept, placebo-controlled, randomized clinical trial, assessing the effect of canagliflozin on cardiac structure and function in patients with advanced renal disease, including those on maintenance dialysis.
Our primary aim is to determine the effect of canagliflozin on cardiac structure and function in patients with advanced chronic kidney disease (CKD), compared with placebo. We hypothesize that canagliflozin will improve left ventricular (LV) hypertrophy in patients with advanced CKD. Our secondary aims are to describe the effect of canagliflozin on other cardiac magnetic resonance imaging parameters and surrogate markers of efficacy in this population.
详细描述
Patients with advanced renal disease, including those on maintenance dialysis, will be randomized to receive canagliflozin 300 mg orally once daily or matching placebo for one year. For patients who are not yet on renal replacement therapy, the study medication will be continued when they transition to dialysis or when they get a kidney transplant.
The prescription of all other medications, including dialysis prescription for dialysis-dependent patients, will be left to the treating physician's discretion. We will discourage changes to medications during follow-up unless deemed clinically necessary. All medications changes will be recorded at each visit.
Symptoms and adverse events will be monitored closely. Participants who experience adverse events classified as severe and probably or definitely related to the study medication will be withdrawn. Patients who develop intercurrent illnesses, are hospitalized, or have surgery (urgent or elective) will temporarily discontinue the drug.
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)
盲法说明
The study will be blinded to study participants and study investigators. Therefore, investigators who will interpret the cardiac magnetic resonance imaging (MRI) and who will adjudicate adverse events will be blinded to treatment group assignment. Canagliflozin 300 mg will be encapsulated to match the placebo.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •advanced CKD, defined as an estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m2 not yet on dialysis OR incident hemodialysis or peritoneal dialysis patients (i.e., who were started on dialysis in the last 6 months)*
- •* For patients who were not previously followed in a CKD clinic and for whom it is not clear whether dialysis was initiated after an acute deterioration in renal function that is potentially reversible, at least 90 days of dialysis will be required prior to enrolment. This criterion only applies to patients for whom baseline eGFR prior to the acute event was ≥ 20 ml/min/1.73m2 or was unknown. The average creatinine values over the last 12 months will be used to calculate baseline eGFR.
- •LV hypertrophy, defined as LV mass > 130 g/m2 in men and 100 g/m2 in females OR hospitalization for heart failure or atherosclerotic cardiovascular (CV) disease in the last 12 months OR type 2 diabetes OR UACR > 200 mg/g on a morning spot urine collection (this criterion is not applicable to patients who are on dialysis and have a urine output < 500 ml per day).
排除标准
- •type 1 diabetes,
- •history of euglycemic ketoacidosis,
- •known hypersensitivity to sodium-glucose cotransporter-2 (SGLT-2) inhibitors,
- •hemodynamic instability (defined as current use of parenteral inotropic agents),
- •systolic BP < 90 mmHg,
- •severe liver cirrhosis (Child-Pugh class C stage),
- •acute hepatitis (defined as an alanine aminotransferase > 2.0 times the upper limit of normal [ULN] or total bilirubin >1.5 times the ULN),
- •recurrent severe genital or urine infections,
- •patients receiving digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if these agents cannot be safely discontinued (due to inhibition of the P-glycoprotein mediated efflux of digoxin by canagliflozin or induction of Uridine 5'-diphospho-glucuronosyltransferase enzymes by the other agents),
- •cardiac MRI-incompatible cardiac devices (cardiac pacemaker, implanted cardiac defibrillator, internal pacing wires, Swan-Ganz catheter, aneurysm clips),
- •claustrophobia,
- •cochlear implants,
- •metallic body in the eyes,
- •pregnancy or breastfeeding,
- •and any other medical condition considered to be a contra-indication by the study physician.
研究组 & 干预措施
Placebo tablet
干预措施: Placebo (Drug)
Canagliflozin (Invokana) 300 mg tablet
干预措施: Canagliflozin 300Mg Tab (Drug)
结局指标
主要结局
Change in left ventricular mass to volume ratio (LVMV) from baseline to 12 months, as assessed by cardiac MRI compared with placebo
时间窗: 12 months
Assessed on cardiac magnetic resonance imaging (MRI)
次要结局
- LV strain parameter changes from baseline to 12 months compared with placebo(12 months)
- Difference in distance in the 6-minute walk test at 12 months from baseline(12 months)
- Difference in dyspnea score at 12 months from baseline(12 months)
- Change in urine albumin to creatinine ratio (UACR) from baseline (only for patients not yet on maintenance dialysis) at 6 and 12 months(6 months and 12 months)
- Change in tubular injury biomarkers(6 months and 12 months)
- Change in dose of erythropoietin-stimulating agents at 12 months from baseline(12 months)
- Change in 24-hour ambulatory blood pressure at 12 months from baseline(12 months)
- Composite of serious adverse events(12 months)
- Changes in left ventricular (LV) and atrial volumes from baseline to 12 months compared with placebo(12 months)
- Changes in myocardial edema and fibrosis from baseline to 12 months compared with placebo(12 months)
- Composite of major adverse cardiovascular events(12 months)
- Death from any cause(12 months)
- Progression to kidney failure (only for patients not yet on maintenance dialysis).(12 months)
- Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)(6 months and 12 months)
- Change in iron profile(6 months and 12 months)
- Difference in quality of life at 12 months from baseline(12 months)
- Change in myocardial oxygenation reserve from baseline to 12 months compared with placebo(12 months)
研究者
Thomas Mavrakanas
Assistant Professor of Medicine
McGill University Health Centre/Research Institute of the McGill University Health Centre