Clinical trial NCT04564833: Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing Coronary Artery Bypass Graft (CABG) and/or Cardiac Valve Surgery (The START Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AKI
Lead sponsor: Renibus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized 1:1:1 to low dose RBT-1, high dose RBT-1, and placebo
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects ≥18 years of age at Screening.
2. Able and willing to comply with all study procedures.
3. Stable kidney function per Investigator assessment and no known episodes of AKI during the preceding 4 weeks.
4. 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.
5. 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.
6. Male subjects must agree not to donate or sell sperm for 30 days following study drug administration.

Exclusion Criteria:

1. Presence of AKI (KDIGO criteria) at the time of Screening.
2. Surgery to be performed without cardiopulmonary bypass.
3. Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature \<28°C (82.4°F).
4. eGFR ≤20 mL/min/1.73m2 or need for dialysis.
5. Surgery for aortic dissection or to correct a major congenital heart defect.
6. Administration of iodinated contrast media within 24 hours prior to cardiac surgery or evidence of contrast-induced nephropathy prior to cardiac surgery.
7. 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.
8. 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.
9. 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.
10. Known or suspected sepsis at time of Screening or confirmed or treated endocarditis within 30 days prior to cardiac surgery.
11. Other current active infection requiring systemic antibiotic treatment.
12. 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.
13. Any congenital coagulation disorder.
14. Asplenia (anatomic or functional).
15. History of photosensitivity or active skin disease that, in the opinion of the Investigator, could be worsened by RBT-1.
16. Known hypersensitivity or previous anaphylaxis to SnPP or any tin-based product.
17. Serum ferritin \>500 ng/mL or those who have received IV iron within 28 days of Screening.
18. Pregnancy or lactation.
19. Treatment with an investigational drug or participation in an interventional study within 30 days prior to administration of study drug.
20. In the opinion of the Investigator, any disease processes or confounding variables that would inappropriately alter the outcome of the study.
21. Inability to comply with the requirements of the study protocol.

Primary outcomes:
measure: Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers
timeFrame: Baseline through Pre-Surgery
Secondary outcomes:
measure: Change in Renal Tubular Injury Biomarkers
timeFrame: Baseline through Day 3 post-cardiac surgery
measure: Number of Subjects With Reduction in Urine Output
timeFrame: Baseline through post-cardiac surgery through Day 5
measure: Number of Subjects With Acute Kidney Injury (AKI)
timeFrame: Baseline through Day 5 post-cardiac surgery
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research, LLC
state: Alabama
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Research Institute, Inc.
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Hospital Anesthesia and Critical Care
state: Illinois
city: Bloomington
country: United States
facility: Indiana University Health Southern Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Lutheran Medical Group
state: Indiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Lansing
country: United States
facility: McLaren Greater Lansing
state: Michigan
city: Midland
country: United States
facility: MyMichigan Medical Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Flushing
country: United States
facility: New York Presbyterian-Queens
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital Center for Clinical Research
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Southport
country: Australia
facility: Gold Cost University Hospital & Health Services
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Saint John
country: Canada
facility: St-John Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec
state: Quebec
Study officials:
References:
citation: Lamy A, Chertow GM, Jessen M, Collar A, Brown CD, Mack CA, Marzouk M, Scavo V, Washburn TB, Savage D, Smith J, Bennetts J, Assi R, Shults C, Arghami A, Butler J, Devereaux PJ, Zager R, Wang C, Snapinn S, Browne A, Rodriguez J, Ruiz S, Singh B; of START Investigators. Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. EClinicalMedicine. 2024 Jan 8;68:102364. doi: 10.1016/j.eclinm.2023.102364. eCollection 2024 Feb.