A Multicenter, Randomized, Open-label Phase II Clinical Trial Evaluating Alprostadil Liposomal Injection in the Prevention of Contrast-induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 132
- 试验地点
- 1
- 主要终点
- Incidence of contrast-induced acute kidney injury within 72 hours after PCI
研究概览
简要总结
This is a multicenter, randomized, open-label phase II clinical trial to evaluate alprostadil liposomal injection in the prevention of contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention.
详细描述
The trial is a multicenter, randomized, open-label, two-stage study. The trial period includes a screening period (up to 14 days), a treatment period (4 days), and a safety follow-up period (7 days ± 3 days). At least 368 patients with pre-PCI (percutaneous coronary intervention) are expected to be included, and all patients will be contrasted with non-ionic hypotonic/isotonic contrast media.
The trail will be divided into two stages. Three dose groups are set in the first stage: 20 µg/day, 40 µg/day and 80 µg/day. In the first stage, on the basis of hydration prevention, patients will randomized to receive 20, 40 or 80 µg/day of alprostadil liposome injection for 4 days (1 to 3 hours before surgery and 3 days after surgery), once a day. The blank control group will only receive hydration prophylaxis. In the second stage, according to the comprehensive evaluation of the data in the first stage, a dose group will be selected to continue to be enrolled. The primary outcome measure is the incidence of contrast-induced acute kidney injury within 72 hours after PCI. During the administration of alprostadil liposomal injection, vital signs, physical examination, ECOG performance status, laboratory test, ECG, adverse events and PK parameters will be evaluated.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Agree to participate in this clinical trial and sign the informed consent voluntarily; 2.18≤age≤80 years old, gender is not limited; 3.Suffering from coronary artery disease and preparing to undergo elective PCI; 4.Serum creatinine>1.5 mg/dL or 30≤eGFR<60 mL/(min·1.73m^2), and meet at least one of the following risk factors:
- •Cardiac function class NYHA class III;
- •Age > 75 years old;
- •Anemia (baseline hematocrit: <36% in women, <39% in men);
排除标准
- •Pre-perform emergency PCI;
- •Previously allergic to alprostadil similar products and contrast agents; used alprostadil within 3 days before the first administration;
- •Severe renal insufficiency: renal replacement therapy may be performed in a short period of time or eGFR<30 mL/(min·1.73m^2);
- •Severe heart failure (LVEF <35% or NYHA class IV), acute heart failure, and pulmonary edema;
- •Requires mechanical circulatory support therapy (intra-aortic balloon pump, catheter-based ventricular assist device, venous-arterial extracorporeal membrane oxygenation therapy, etc.);
- •Hypotension: systolic blood pressure < 90 mmHg;
- •Acute bleeding disorders or bleeding tendency, and the investigators believe that they are not suitable to participate in this trial;
- •Severe anemia (hemoglobin <60 g/L);
- •Active hepatitis B virus infection (positive hepatitis B virus surface antigen and the quantitative detection value of hepatitis B virus DNA exceeds the upper limit of the normal range of the research center), positive for any one of hepatitis C virus antibody, HIV antibody, and Treponema pallidum antibody;
- •Abnormal liver function (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal);
- •Contrast agents or known nephrotoxic drugs (aminoglycoside antibiotics, amphotericin B, vancomycin, antiviral drugs, non-steroidal anti-inflammatory drugs (except aspirin), Immunosuppressants, traditional Chinese medicines and proprietary Chinese medicines containing aristolochic acid, etc.) within 14 days before the first application of the test drug, or the use of drugs that protect the kidneys against AKI (N-acetylcysteine, sodium bicarbonate, aminophylline) within 3 days before the first application of the test drug;
- •Severe renal artery stenosis, and in the opinion of the the investigator, is unsuitable to participate in this trial;
- •Electrolyte disorders (serum potassium <2.5 mmol/L or serum sodium <125 mmol/L);
- •A history of glaucoma or ocular hypertension or gastric ulcer;
- •Interstitial pneumonia or mental illness or dementia;
- •Malignant tumors;
- •Have participated in drug clinical trials and used drugs within 3 months before screening;
- •Pregnant or breastfeeding, or patients who cannot use effective contraception during the study;
- •Other patients deemed unsuitable for participation in this trial by the investigator.
研究组 & 干预措施
20 µg group
Patients will receive alprostadil liposome injection at 20 µg once daily (QD) for 4 days (1 to 3 hours before surgery and 3 days after surgery).
干预措施: Alprostadil liposome injection (Drug)
40 µg group
Patients will receive alprostadil liposome injection at 40 µg once daily (QD) for 4 days (1 to 3 hours before surgery and 3 days after surgery)
干预措施: Alprostadil liposome injection (Drug)
80 µg group
Patients will receive alprostadil liposome injection at 80 µg once daily (QD) for 4 days (1 to 3 hours before surgery and 3 days after surgery)
干预措施: Alprostadil liposome injection (Drug)
结局指标
主要结局
Incidence of contrast-induced acute kidney injury within 72 hours after PCI
时间窗: from baseline to 72 hours after PCI
Incidence of contrast-induced acute kidney injury within 72 hours after PCI
次要结局
- Changes in blood urea nitrogen from baseline at 24 hours, 48 hours, and 72 hours after angiography(from baseline to 72 hours after angiography)
- Incidence of major adverse cardiovascular events (MACE) during the study period (recurrent angina, nonfatal myocardial infarction, acute heart failure, ventricular fibrillation, cardiac death)(from baseline to 7 days after last dose)
- Changes in serum creatinine from baseline at 24 hours, 48 hours, and 72 hours after angiography(from baseline to 72 hours after angiography)
- Incidence of renal replacement therapy after angiography during the study period(from baseline to 7 days after last dose)
- Changes in IL-6 from baseline at 24 hours, 48 hours, and 72 hours after angiography(from baseline to 72 hours after angiography)
- Adverse events(from baseline to 7 days after last dose)
- Changes in cystatin C from baseline at 24 hours, 48 hours, and 72 hours after angiography(from baseline to 72 hours after angiography)
- Changes in hs-CRP from baseline at 24 hours, 48 hours, and 72 hours after angiography(from baseline to 72 hours after angiography)