Cardiac Surgery Associated - Acute Kidney Injury, Ischemia Reperfusion Injury
Conditions
Brief summary
This is a Randomized, Single-blind, Multi-center, Placebo-controlled, Phase 2a clinical trial of BX-001N to prevent patients from Cardiac Surgery Associated Acute Kidney Injury (CSA-AKI) and subsequent Major Adverse Kidney Events (MAKE) in approximately 50 participants.
Detailed description
This study will enroll approximately 50 participants, with 16 participants randomized to Experimental Group 1 and 4 participants to the Placebo Group 1, 15 participants to Experimental Group 2 and 15 participants to the Placebo Group 2. Randomized participants will be hospitalized from one day prior to surgery (Baseline, Day -1) through Day 7. Investigational product (IP) (i.e., BX-001N) will be administered intravenously at a weight-based dose as follows: The test drug will be administered three times in total. Participants in the Placebo Group will receive placebo at the same time points and in the same manner. Follow-up visits will be conducted up to Day 90 at the study site for scheduled efficacy and safety assessments.
Interventions
DRUGBX-001N Experimental group 1
Each participant will receive BX-001N at a weight-based low dose via IV injection once daily for a total of three administrations.
DRUGBX-001N Experimental group 2
Each participant will receive BX-001N at a weight-based high dose via IV injection once daily at the same time during hospitalization, for a total of three administrations.
DRUGPlacebo group 1
Each participant will receive Placebo at a weight-based dose via IV injection once daily at the same time during hospitalization, for a total of three administrations.
DRUGPlacebo group 2
Each participant will receive Placebo at a weight-based dose via IV injection once daily at the same time during hospitalization, for a total of three administrations.
Sponsors
Bilix Co.,Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
19 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. 19 to 90 years of age 2. Participants with aortic disease scheduled for cardiac surgery via total circulatory arrest (TCA) 3. Body weight ≥ 30 kg 4. Participants with vital signs within the following ranges * Temperature : 35.0\~37.5°C * Blood pressure : Systolic blood pressure(SBP) 100\~160 mmHg, Diastolic blood pressure(DBP) \< 100 mmHg * Pulse : 50\~100 bpm (regardless of drug use) 5. Willing to comply with the schedule and sign the informed consent 6. Participants with moderate renal impairement
Exclusion criteria
1. Participants scheduled for emergent or salvage cardiac surgery 2. Use of kidney replacement therapy (KRT) or presence of acute kidney injury (AKI) 3. Participants at risk of bleeding 4. Participants who underwent cardiac surgery via mid-sternotomy or thoracotomy, including major congenital heart disease 5. Participants who received cardiopulmonary resuscitation within 30 days prior to cardiac surgery 6. Recipient of a solid organ or bone marrow transplantation 7. Participants with cardiogenic shock or hemodynamics instability, or planned use of intra-aortic balloon pump, extracorporeal membrane oxygenation, or left ventricular assist device 8. Active systemic bacterial, viral, or fungal infection 9. History of HIV 10. Positive serology test for HAV, HBV, HCV or Syphilis 11. Participants with impaired liver function due to cirrhosis, or those with 2x UNR blood levels of ALP, AST, or ALT, or with total bilirubin levels outside the normal range 12. Uncontrolled hypertension 13. History of congenital immunodeficiency 14. Genetic disorder with severe and abnormal bilirubin metabolism 15. Participants deemed unsuitable for the study in the discretion of the investigator 16. History of malignancy 17. Planned use of any pharmacologic agent other than the IP assigned in this study for the prevention or treatment of acute kidney injury 18. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents 19. History of participation in other clinical trials within 30 days 20. Presence of a do-not-resuscitate order or life expectancy of \< 3 months 21. Female subjects of childbearing potential 22. Male subjects and their spouse/partner are not willing to use appropriate contraception, or if their spouse/partner is pregnant, breastfeeding or has a plan 23. Poorly controlled type 2 diabetes mellitus 24. New York Heart Association (NYHA) Class IV heart failure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in NGAL levels | Baseline(Day -1) to Day 7 |
| Change from baseline in sCr levels | Baseline(Day -1) to Day 7 |
| Change from baseline in eGFR | Baseline(Day -1) to Day 30 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in CysC | Baseline(Day -1) to Day 7 | — |
| Change from baseline in TIMP-2 | Baseline(Day -1) to Day 7 | — |
| Change from baseline in IGFBP7 | Baseline(Day -1) to Day 7 | — |
| Collection of Major Adverse Renal Events [MAKE] | Up to Day 90 | — |
| Change from baseline in Incidence of AKI based on Kidney Disease: Improving Global Outcomes [KDIGO] criteria | Baseline(Day -1) to Day 7 | \[Staging of AKI\] Stage 1 : 1.5-1.9 times baseline or ≥0.3mg/dL increase Stage 2 : 2.0-2.9 times baseline Stage 3 : 3.0 times baseline or increase in serum creatinine to ≥4.0mg/dL or Initiation of renal replacement therapy |
| Change from baseline in BUN | Baseline(Day -1) to Day 30 | — |
Countries
South Korea
Contacts
CONTACTChoonmo Kang
CONTACTSoobin Son
STUDY_CHAIRMyung Lip Kim, Chief Executive Officer
Bilix Co.,Ltd.
Outcome results
None listed