Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery
- Conditions
- AKI
- Interventions
- Drug: High Dose RBT-1Drug: PlaceboDrug: Low Dose RBT-1
- Registration Number
- NCT04564833
- Lead Sponsor
- Renibus Therapeutics, Inc.
- Brief Summary
The purpose of this study is to evaluate the effect of RBT-1 (stannous protoporphyrin \[SnPP\]/iron sucrose \[FeS\]) on preconditioning response biomarkers in subjects who are at risk for AKI following cardiac surgery.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 152
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Male or female subjects ≥18 years of age at Screening.
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Able and willing to comply with all study procedures.
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Stable kidney function per Investigator assessment and no known episodes of AKI during the preceding 4 weeks.
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Scheduled to undergo non-emergent coronary and/or valve surgery(ies) requiring cardiopulmonary bypass, including:
- CABG alone;
- Combined CABG surgery/repair of 1 or more cardiac valves;
- Cardiac valve(s) replacement or repair alone.
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Females and males of childbearing potential must agree to use 2 forms of contraception, with at least 1 being a barrier method, or abstain from sexual activity for 30 days following study drug administration.
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Male subjects must agree not to donate or sell sperm for 30 days following study drug administration.
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Presence of AKI (KDIGO criteria) at the time of Screening.
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Surgery to be performed without cardiopulmonary bypass.
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Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature <28°C (82.4°F).
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eGFR ≤20 mL/min/1.73m2 or need for dialysis.
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Surgery for aortic dissection or to correct a major congenital heart defect.
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Administration of iodinated contrast media within 24 hours prior to cardiac surgery or evidence of contrast-induced nephropathy prior to cardiac surgery.
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Cardiogenic shock or hemodynamic instability within the 24 hours prior to surgery and requirement for inotropes or vasopressors or other mechanical devices, such as intra-aortic balloon counter-pulsation.
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Requirement for any of the following within 7 days prior to cardiac surgery:
- Defibrillator or permanent pacemaker;
- Mechanical ventilation;
- Intra-aortic balloon counter-pulsation;
- Left ventricular assist device;
- Other forms of mechanical circulatory support.
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Known history of cancer within the past 2 years, except for carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin.
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Known or suspected sepsis at time of Screening or confirmed or treated endocarditis within 30 days prior to cardiac surgery.
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Other current active infection requiring systemic antibiotic treatment.
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Inadequate hepatic function, defined as total bilirubin or alanine aminotransferase or aspartate aminotransferase >2X the upper limit of normal at time of Screening or Child Pugh Class C liver disease or higher.
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Any congenital coagulation disorder.
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Asplenia (anatomic or functional).
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History of photosensitivity or active skin disease that, in the opinion of the Investigator, could be worsened by RBT-1.
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Known hypersensitivity or previous anaphylaxis to SnPP or any tin-based product.
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Serum ferritin >500 ng/mL or those who have received IV iron within 28 days of Screening.
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Pregnancy or lactation.
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Treatment with an investigational drug or participation in an interventional study within 30 days prior to administration of study drug.
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In the opinion of the Investigator, any disease processes or confounding variables that would inappropriately alter the outcome of the study.
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Inability to comply with the requirements of the study protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High Dose RBT-1 High Dose RBT-1 Single IV infusion prior to cardiac surgery Placebo Placebo Single IV infusion prior to cardiac surgery Low Dose RBT-1 Low Dose RBT-1 Single IV infusion prior to cardiac surgery
- Primary Outcome Measures
Name Time Method Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers Baseline through Pre-Surgery Composite of the geometric mean of the ratios of the maximum PreOp value over Baseline for plasma heme oxygenase-1 (HO-1), ferritin, and interleukin-10 (IL-10)
- Secondary Outcome Measures
Name Time Method Change in Renal Tubular Injury Biomarkers Baseline through Day 3 post-cardiac surgery Geometric mean of the ratios of the maximum PostOp value over Baseline for urine KIM-1, NGAL, and cystatin C.
Number of Subjects With Reduction in Urine Output Baseline through post-cardiac surgery through Day 5 Documented AE of sustained reduction in urine output, oliguria, or anuria post-cardiac surgery through Day 5
Number of Subjects With Acute Kidney Injury (AKI) Baseline through Day 5 post-cardiac surgery AKI is defined using the KDIGO criteria (ie, an absolute increase in serum creatinine of ≥1.5 × Baseline; or documented AE of sustained reduction in urine output, oliguria, or anuria; or initiation of dialysis).
Trial Locations
- Locations (25)
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
McLaren Greater Lansing
🇺🇸Lansing, Michigan, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Rochester General Hospital Center for Clinical Research
🇺🇸Rochester, New York, United States
Indiana University Health Southern Indiana
🇺🇸Bloomington, Indiana, United States
St-John Regional Hospital
🇨🇦Saint John, New Brunswick, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec
🇨🇦Québec, Quebec, Canada
MyMichigan Medical Center
🇺🇸Midland, Michigan, United States
Lutheran Medical Group
🇺🇸Fort Wayne, Indiana, United States
Heart Center Research, LLC
🇺🇸Huntsville, Alabama, United States
MedStar Health Research Institute, Inc.
🇺🇸Washington, District of Columbia, United States
Gold Cost University Hospital & Health Services
🇦🇺Southport, Queensland, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Santa Barbara Cottage Hospital
🇺🇸Santa Barbara, California, United States
University of Chicago Hospital Anesthesia and Critical Care
🇺🇸Chicago, Illinois, United States
New York Presbyterian-Queens
🇺🇸Flushing, New York, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Hamilton Health Sciences Corporation
🇨🇦Hamilton, Ontario, Canada
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia