Renal Insufficiency Following Contrast Media Administration Trial II (Remedial II): The RenalGuard System in High-Risk Patients for Contrast-Induced Acute Kidney Injury
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 294
- 试验地点
- 4
- 主要终点
- Number of Participants With Contrast-induced Acute Kidney Injury
研究概览
简要总结
The purpose of the present study is to assess the role of the RenalGuard System as compared to the optimal strategy (sodium bicarbonate infusion plus N-acetylcysteine (NAC)) in high and very-high risk patients to prevent contrast-induced acute kidney injury contrast induced acute kidney injury (CI-AKI).
Consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, will be randomly assigned to 1) prophylactic administration of sodium bicarbonate plus NAC (Systemic alone therapy group; n > 133) and 2) RenalGuard System treatment (RenalGuard group; n > 133). All enrolled patients must have an estimated glomerular filtration rate <30 ml/min/1.73 m2 and/or a contrast nephropathy risk score ≥11). In all cases iodixanol (an iso-osmolar, non ionic contrast agent) will be administered. The primary end point is an increase of >=0.3 mg/dL in the creatinine concentration 48 hours after the procedure.
This study will give important answers on how to prevent CI-AKI in high and very-high risk patients undergoing contrast media exposure.
详细描述
The strategy of volume supplementation by sodium bicarbonate plus N-acetylcysteine (NAC) seems to be the optimal pharmacological approach in preventing contrast induced acute kidney injury (CI-AKI) in patients at medium-to-high risk. Whether this prophylactic strategy is effective in high and very-high risk patients is unknown. In this subset of patients the potential protective effects and therapeutic advantage of a local delivery of protective compounds should be investigated. The RenalGuard™ System (PLC Medical Systes, Inc.) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard Therapy. The RenalGuard Therapy is based on the theory that creating and maintaining a high urine output is beneficial to patients undergoing imaging procedures where contrast agents are used. This should allow the body to rapidly eliminate contrast, reducing its toxic effects. The RenalGuard System seems to be ideal for the prevention of CI-AKI, by allowing an optimal urine flow rate >150 ml/h (ideally >300 ml/h). Preliminary data suggests that the RenalGuard System, by increasing the urine flow rate ≥ 300 ml/h, allows a quick renal first-pass elimination and therefore reduces the risk for contrast nephropathy. The potential benefits of RenalGuard Therapy are intended to reduce the incidence of CI-AKI via a combination of known physiological effects of high urine output including: a) lower concentration of contrast in the kidneys, b) more rapid transit of contrast through the kidneys, c) less overall exposure to toxic contrast, d) potential reduction of oxygen consumption in the medulla of the kidneys. No randomized study has been performed to assess the role of the RenalGuard System as compared to the optimal strategy (sodium bicarbonate infusion plus NAC) in high and very-high risk patients to prevent CI-AKI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Age >=18 years
- •Chronic kidney disease (estimated glomerular filtration rate <=30 ml/min/1.72 m2) and/or
- •Risk score for contrast nephropathy ≥11 (according to the Mehran score; J Am Coll Cardiol 2004; 44: 1393-1399)
排除标准
- •Heart failure (NYHA functional class III-IV)
- •Acute pulmonary edema
- •Acute myocardial infarction
- •Recent (<=2 days) contrast media exposure
- •Patients enrolled in concomitant studies
- •Administration of theophylline, dopamine, mannitol and fenoldopam.
- •End-stage CKD (patients on chronic dialysis)
- •Systemic hypotension (systolic blood pressure < 100 mg/dl).
- •Multiple myeloma
研究组 & 干预措施
Systemic alone therapy group
Systemic alone therapy group will be treated by intravenous sodium bicarbonate plus NAC administration. Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. (9) The initial i.v. bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.
干预措施: Systemic alone therapy (Drug)
RenalGuard System group
Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow <300 ml/h.
干预措施: RenalGuard system (Device)
结局指标
主要结局
Number of Participants With Contrast-induced Acute Kidney Injury
时间窗: at 48 hours following contrast exposure
The primary outcome measure will be the rate of development of CI-AKI in the 2 study arms (number of participants). CI-AKI is defined as an increase in the serum creatinine concentration \>=0.3 mg/dL from the baseline value at 48 hours after administration of the contrast media or the need for dialysis.
次要结局
- Changes in the Serum Cystatin C Concentration at 24 and 48 Hours After Contrast Exposure(7 days)
- The Rate of In-hospital Major Adverse Events (i.e. Acute Myocardial Infarction, c) Renal Failure Requiring Dialysis, and d) Acute Pulmonary Edema)(1 month)
- the Rate of Acute Renal Failure Requiring Dialysis(1 month)
- The Cost-effectiveness Ratio.(1 month)
- Rate of Kidney Injury and Major Adverse Events(7 days)
- Changes in the Urine and Serum NGAL Concentration After Contrast Exposure(7 days)
研究者
Carlo Briguori
MD, PhD
Clinica Mediterranea