RAvulizumab to PRotect PaTients with Chronic Kidney DisEase (CKD) froM Cardiac Surgery Associated Acute Kidney Injury (CSA-AKI) and Subsequent Major Adverse Kidney Events (MAKE): A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Enrollment
- 736
- Locations
- 7
- Primary Endpoint
- To assess the efficacy of ravulizumab in reducing risk of MAKE90 following CPB
Overview
Brief Summary
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study of ravulizumab in adult participants with CKD and stable cardiac disease undergoing non-emergent sternotomy with CPB for coronary artery bypass graft (CABG), valve replacement or repair, or combined procedure, to reduce the risk of post-operative AKI and subsequent MAKE at 90 days after surgery. Participants considered at risk for AKI after CPB have estimated glomerular filtration rate (eGFR) ≥ 20 to < 60 mL/min/1.73 m2 with minimum Society of Thoracic Surgeons (STS) Calculator Renal Failure Risk Score of 2.8%.
The study consists of a Screening Period of up to 28 days with Randomization and Dosing within 1 to 7 days prior to surgery with CPB, a 90-day Primary Evaluation Period post CPB, and a Survival Follow-up including assessment of KRT status at 365 days post CPB.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- Participant, Investigator and Outcome Assessor Blinded
Eligibility Criteria
- Ages
- 18.00 Year(s) to 90.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Greater than or equal to 18 to less than or equal to 90 years of age at the time of signing the informed consent.
- •Male or female.
- •Body weight greater than or equal 30 kg at Screening.
- •Planned non-emergent sternotomy with CPB procedure for the following surgeries i.
- •Multi-vessel CABG ii.
- •Valve replacement or repair; ascending aorta surgery permitted if combined with aortic valve replacement or repair iii.
- •Combined CABG and valve surgery; inclusion of single-vessel CABG when combined with valve replacement or repair is permitted.
- •Known CKD for at least 90 days with eGFR Greaterthan or equal to 20 to less than 60 mL min 1.73 m2 CKD Stage 3A, 3B, or 4 at Screening
- •At risk for postsurgical AKI as defined by a minimum STS Calculator Renal Failure Risk Score of 3 percentage assessed at time of screening.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
Exclusion Criteria
- •Emergency or salvage cardiac surgery is expected at screening or randomization, as assessed by the Investigator
- •Single-vessel CABG without valve surgery is planned.
- •Off-pump surgery is planned (eg, surgery without CPB).
- •Any use of KRT or presence of AKI within 30 days of randomization (AKI defined as 1.5× increase in sCr over baseline), except transient (less than or equal to 5 days) Stage 1 AKI after iodinated contrast exposure
- •Recipient of a solid organ or bone marrow transplantation.
- •Cardiogenic shock, hemodynamic instability, use of intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation, or left ventricular assist device within 72 hours of randomization.
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.
- •Congenital immunodeficiency.
- •History of unexplained, recurrent infection.
- •Known medical or psychological condition(s), including substance abuse, or risk factor that, in the opinion of the Investigator, might interfere with the participant s full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.
Outcomes
Primary Outcomes
To assess the efficacy of ravulizumab in reducing risk of MAKE90 following CPB
Time Frame: To assess the efficacy of ravulizumab in reducing risk of MAKE90 following CPB at DAY 90 post CPB.
Adult participants with CKD as defined by the inclusion and exclusion criteria
Time Frame: To assess the efficacy of ravulizumab in reducing risk of MAKE90 following CPB at DAY 90 post CPB.
Secondary Outcomes
- Immunogenicity
- Safety:
- To assess the efficacy of ravulizumab in reducing risk of AKI (based on sCr) following CPB(1) CSA-AKI free at Day 90 post CPB)
- Other Secondary Efficacy(To assess the efficacy of ravulizumab in reducing risk of MAKE, MAKE (based on sCr), AKI (based on sCr), and related outcomes)
- Other Secondary Efficacy(To assess the efficacy of ravulizumab in reducing risk of MAKE, MAKE (based on sCr), AKI (based on sCr), and related outcomes contd..)
- Healthcare Resource Utilization
- Health-related QoL(To assess the effect of ravulizumab on quality of life in participants with CKD undergoing non-emergent CPB.)
- PK and PD(To evaluate PK and PD of ravulizumab in participants with CKD undergoing non-emergent CPB)
- Exploratory(To assess biomarkers at baseline and change in response to treatment)
Investigators
Dr Santosh Kadam
AstraZeneca Pharma India Ltd.