A Study to Explore the Efficacy of Alprostadil Liposomes Injection in the Prevention of CI-AKI

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Contrast-induced Acute Kidney Injury

Intervention / Treatment
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* Drug: Alprostadil liposome injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 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); Diabetes. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 µg group<br>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). | Drug: Alprostadil liposome injection<br>* Alprostadil liposome injection, iv drip, QD×4 days (1 to 3 hours before surgery and 3 days after surgery)<br>* Other names: Alprostadil liposome;|
| Experimental: 40 µg group<br>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) | Drug: Alprostadil liposome injection<br>* Alprostadil liposome injection, iv drip, QD×4 days (1 to 3 hours before surgery and 3 days after surgery)<br>* Other names: Alprostadil liposome;|
| Experimental: 80 µg group<br>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) | Drug: Alprostadil liposome injection<br>* Alprostadil liposome injection, iv drip, QD×4 days (1 to 3 hours before surgery and 3 days after surgery)<br>* Other names: Alprostadil liposome;|
| No Intervention: blank control group<br>Patients will receive only basic hydration therapy which the experimental groups will receive. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of contrast-induced acute kidney injury within 72 hours after PCI | Incidence of contrast-induced acute kidney injury within 72 hours after PCI | from baseline to 72 hours after PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum creatinine from baseline at 24 hours, 48 hours, and 72 hours after angiography | Changes in serum creatinine from baseline at 24 hours, 48 hours, and 72 hours after angiography | from baseline to 72 hours after angiography | 
| Changes in blood urea nitrogen from baseline at 24 hours, 48 hours, and 72 hours after angiography | Changes in blood urea nitrogen from baseline at 24 hours, 48 hours, and 72 hours after angiography | from baseline to 72 hours after angiography | 
| Changes in cystatin C from baseline at 24 hours, 48 hours, and 72 hours after angiography | 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 | Changes in hs-CRP from baseline at 24 hours, 48 hours, and 72 hours after angiography | from baseline to 72 hours after angiography | 
| Changes in IL-6 from baseline at 24 hours, 48 hours, and 72 hours after angiography | Changes in IL-6 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 | Incidence of renal replacement therapy after angiography during the study | from baseline to 7 days after last dose | 
| Adverse events | Adverse events from baseline to 7 days after last dose, including symptoms, Abnormal laboratory test | from baseline to 7 days after last dose | 
| Incidence of major adverse cardiovascular events (MACE) during the study period (recurrent angina, nonfatal myocardial infarction, acute heart failure, ventricular fibrillation, cardiac death) | 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 |