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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Contrast-induced Acute Kidney Injury
• Intervention / Treatment: Drug: Alprostadil liposome injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 368
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yong Huo, Professor; Phone Number: +86-010-83572283; Email: huoyong@263.net.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Beijing University First Hospital
      • Contact: Yong Huo, Professor; Phone Number: +86-010-83572283; Email: huoyong@263.net.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Cardiac function class NYHA class III;
2. Age > 75 years old;
3. Anemia (baseline hematocrit: <36% in women, <39% in men);
4. Diabetes.

Exclusion Criteria:

1. Pre-perform emergency PCI;
2. Previously allergic to alprostadil similar products and contrast agents; used alprostadil within 3 days before the first administration;
3. Severe renal insufficiency: renal replacement therapy may be performed in a short period of time or eGFR<30 mL/(min·1.73m^2);
4. Severe heart failure (LVEF <35% or NYHA class IV), acute heart failure, and pulmonary edema;
5. Requires mechanical circulatory support therapy (intra-aortic balloon pump, catheter-based ventricular assist device, venous-arterial extracorporeal membrane oxygenation therapy, etc.);
6. Hypotension: systolic blood pressure < 90 mmHg;
7. Acute bleeding disorders or bleeding tendency, and the investigators believe that they are not suitable to participate in this trial;
8. Severe anemia (hemoglobin <60 g/L);
9. 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;
10. Abnormal liver function (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal);
11. 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;
12. Severe renal artery stenosis, and in the opinion of the the investigator, is unsuitable to participate in this trial;
13. Electrolyte disorders (serum potassium <2.5 mmol/L or serum sodium <125 mmol/L);
14. A history of glaucoma or ocular hypertension or gastric ulcer;
15. Interstitial pneumonia or mental illness or dementia;
16. Malignant tumors;
17. Have participated in drug clinical trials and used drugs within 3 months before screening;
18. Pregnant or breastfeeding, or patients who cannot use effective contraception during the study;
19. Other patients deemed unsuitable for participation in this trial by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Alprostadil liposome injection; Alprostadil liposome injection, iv drip, QD×4 days (1 to 3 hours before surgery and 3 days after surgery); Other Names: Alprostadil liposome
Experimental: 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)	Drug: Alprostadil liposome injection; Alprostadil liposome injection, iv drip, QD×4 days (1 to 3 hours before surgery and 3 days after surgery); Other Names: Alprostadil liposome
Experimental: 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)	Drug: Alprostadil liposome injection; Alprostadil liposome injection, iv drip, QD×4 days (1 to 3 hours before surgery and 3 days after surgery); Other Names: Alprostadil liposome
No Intervention: blank control group; Patients will receive only basic hydration therapy which the experimental groups will receive.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Study Director: Wen Xu, Derector, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 25, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Vasodilator Agents; Urological Agents; Platelet Aggregation Inhibitors; Alprostadil
• Other Study ID Numbers: HF1307-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No