Renal Insufficiency Following Contrast Media Administration Trial III (REMEDIAL III): Renalguard System Versus Left-ventricular End-diastolic Pressure-guided Hydration in High-risk Patients for Contrast-induced Acute Kidney Injury
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 700
- 主要终点
- Composite of 1) development of CI-AKI, and/or acute pulmonary edema.
研究概览
简要总结
The urine flow rate (UFR)-guided and the left-ventricular end-diastolic pressure (LVEDP)-guided hydration regimens have been proposed to prevent contrast-induced acute kidney injury (CI-AKI). The REnal Insufficiency Following Contrast MEDIA Administration TriaL III (REMEDIAL III) trial is a randomized, multicenter, investigator-sponsored trial aiming to compare these 2 hydration strategies in high risk patients.
Patients with estimated glomerular filtration rate <45 ml/min/1.73 m2 and/or a high risk for CI-AKI (as defined according to both Mehran's score ≥11 and/or Gurm's score >7) will be enrolled. Patients will be divided in high (>12 mm Hg) and normal LVEDP, non-invasively estimated by transmitral flow velocity to annular velocity ratio (E/E' index). Patients in each group will be randomly assigned to 1) LVEDP-guided hydration with normal saline (LVEDP-guided group). The fluid infusion rate will be adjusted according to the LVEDP as follows: 5 mL/kg/hr for LVEDP <12 mmHg; 3 mL/kg/hr for 13-18 mmHg; and 1.5 mL/kg/hr for >18 mmHg. 2) UFR-rate guided hydration (RenalGuard group). In this group, hydration with normal saline plus low-dose of furosemide is controlled by the RenalGuard system, in order to reach and maintain a high (>300 mL/h) UFR. In all cases iobitridol (an low-osmolar, non ionic contrast agent) will be administered. The primary endpoint is the composite of CI-AKI (i.e., serum creatinine increase ≥ 25% and ≥ 0.5 mg/dl from the baseline value at 48 hours after contrast media exposure) and/or acute pulmonary edema.
详细描述
Contrast-induced acute kidney injury (CI-AKI) is a powerful predictor of unfavorable early and late outcome. Hydration represents the cornerstone in CI-AKI prevention1. However, at present there is no consensus on how hydration should be carried out. The most recommended hydration regimen is normal saline infusion at 1 mL/kg/h 12 hours before and 12 hours after CM exposure. Limitations of this hydration regimen include 1) preclusion in urgent/emergent settings, and 2) suboptimal efficacy in high- and very high risk patients. Indeed, in high and very-high risk patients the rate of CI-AKI may be still high, whereas a forced hydration regimen may increase the risk of pulmonary edema.
In order to clarify how to carry out optimal hydration, 2 regimens have been recently proposed: 1) left ventricular end-diastolic pressure (LVEDP)-guided hydration and 2) urine flow rate (UFR)-guided hydration. The POSEIDON trial demonstrated that the left ventricular end-diastolic pressure (LVEDP)-guided hydration is superior to the conventional hydration regimen in preventing CI-AKI. In the LVEDP-guided hydration, the fluid infusion rate was adjusted according to the LVEDP as follows: 5 mL/kg/hr for LVEDP <12 mmHg; 3 mL/kg/hr for 13-18 mmHg; and 1.5 mL/kg/hr for >18 mmHg. The reported rate of pulmonary edema was 1.5%.
Another theory for CI-AKI prophylaxis suggests to induction and maintenance of a high UFR. This high UFR should allow the body to rapidly eliminate contrast media, reducing contact time within nephron. The RenalGuard™ System (PLC Medical Systems, Inc.) in combination with limited (0.25 mg/kg) dose of furosemide induces an maintains a high UFR (>300 mL/h) safely by maintaining the intravascular blood volume and minimizing the risk of over or under-hydration. Furthermore, the reported rate of pulmonary edema was <1%.
The purpose of the present study is to compare the LVEDP-guided hydration and the UFR-guided hydration in patients at high risk for CI-AKI.
Following enrollment, patients will be randomly assigned to one of the following treatments: 1) LVEDP-guided group, and 2) RenalGuard group. Enrolled patients will be stratified, according to the estimated LVEDP value, into high LVEDP and normal LVEDP group. LVEDP will be non-invasively estimated by the transmitral flow velocity to annular velocity ratio (E/E' index). Estimated LVEDP pressure >12 mm Hg will be considered high. Patients allocated in both groups will receive intravenous 0.9% sodium chloride for at least one hour prior to cardiac catheterization. In both groups the fluid rate will be adjusted according to the non-invasive LVEDP estimate as follows: 5 mL/kg/hr for LVEDP ≤12 mmHg; 3 mL/kg/hr for 13-18 mmHg; and 1.5 mL/kg/h for >18 mmHg, as suggested in the POSEIDON trial. Invasive LVEDP measurement will be also estimated in all patients by placing an angled 5 or 6-French pigtail catheter in the mid-cavity of the left ventricle at the beginning of the procedure and before contrast media injection in order to confirm the non-invasive estimated value.
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
- Double (Participant, Outcomes Assessor)
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
- •All consecutive patients with chronic kidney disease (CKD) scheduled for coronary and/or peripheral angiography and/or angioplasty with an eGFR <45 ml/min/1.73 m2 and/or
- •At high risk for CI-AKI according to Mehran's score ≥11 and/or Gurm's score >7
排除标准
- •Age <18 years
- •Women who are pregnant
- •Acute pulmonary edema
- •Acute myocardial infarction
- •Recent contrast media exposure
- •End-stage CKD on chronic dialysis
- •Multiple myeloma
- •Current enrolment in any other study when enrolment in the REMEDIAL III would involve deviation from either protocol
- •Cardiogenic shock
- •Administration of theophilline, dopamine, mannitol and fenoldopam
研究组 & 干预措施
LVEDP-guided group
Patients allocated to the LVEDP-guided group will continue to receive intravenous 0.9% sodium chloride, according to the protocol suggested in the POSEIDON trial (that is, 5 mL/kg/hr for LVEDP ≤12 mmHg; 3 mL/kg/hr for 13-18 mmHg; and 1.5 mL/kg/h for >18 mmHg). The fluid rate will be eventually modified at the start of the procedure in case of discordance between non-invasive and invasive LVEDP pressure estimate, being the invasive value considered as gold-standard. The fluid rate will continued during the procedure, and for 4 hours post-procedure.
Renalguard group
Patients enrolled in this group will be treated by hydration with 0.9% saline controlled by the RenalGuard system. On top of the 1.5-5.0 ml/kg/h that patients would have received over the previous hour (according to the non-invasive estimate LVEDP), an initial bolus of 250 ml will be administered. In case of LV ejection fraction ≤30% and/or LVEDP >18 mm Hg the bolus will 150 mL. Therefore, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow rate (≥300 mL/h). The controlled hydration by the RenalGuard system will be continued during the procedure and for 4 hours following the procedure. Urine flow rate is monitored and maintained at the target value through the procedure and during the following 4 hours. Additional furosemide doses are allowed in case of decrease of the urine flow rate below the target value.
干预措施: RenalGuard system™® (PLC Medical Systems, Inc. Franklin, MA, USA) (Device)
结局指标
主要结局
Composite of 1) development of CI-AKI, and/or acute pulmonary edema.
时间窗: within 48 hours after contrast media exposure
The primary outcome measure is composite of 1) development of CI-AKI, and/or acute pulmonary edema. CI-AKI is defined as an increase in the serum creatinine concentration \>=25% and \>=0.5 mg/dl from the baseline value at 48 hours after administration of the contrast media or the need for dialysis
次要结局
- Cystatin C change(48 hours)
- Major adverse event rate(12 months)
- Impact of LVEDP(48 hours)
- Dialysis rate(5 days)
- Creatinine change(48 hours)
- Length of in-hospital stay (LOS)(30 days)
研究者
Carlo Briguori
MD, PhD
Clinica Mediterranea