Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery

AKI Clinical Trial

— START  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04564833
• Other study ID #: REN-004
• Status: Completed
• Phase: Phase 2
• Start date: August 4, 2021
• Est. completion date: February 3, 2023

Study information

• Verified date: April 2024
• Source: Renibus Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: February 3, 2023
• Est. primary completion date: November 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• AKI

Intervention

Drug:
• Low Dose RBT-1
intravenous administration
• High Dose RBT-1
intravenous administration
• Placebo
intravenous administration

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Gold Cost University Hospital & Health Services	Southport	Queensland
Canada	Hamilton Health Sciences Corporation	Hamilton	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec	Québec	Quebec
Canada	St-John Regional Hospital	Saint John	New Brunswick
United States	Indiana University Health Southern Indiana	Bloomington	Indiana
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of Chicago Hospital Anesthesia and Critical Care	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	New York Presbyterian-Queens	Flushing	New York
United States	Lutheran Medical Group	Fort Wayne	Indiana
United States	Heart Center Research, LLC	Huntsville	Alabama
United States	McLaren Greater Lansing	Lansing	Michigan
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Keck Hospital of USC	Los Angeles	California
United States	MyMichigan Medical Center	Midland	Michigan
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Irving Medical Center	New York	New York
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Rochester General Hospital Center for Clinical Research	Rochester	New York
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Stanford University Medical Center	Stanford	California
United States	MedStar Health Research Institute, Inc.	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Renibus Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (1)

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 In — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers	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)	Baseline through Pre-Surgery
Secondary	Change in Renal Tubular Injury Biomarkers	Geometric mean of the ratios of the maximum PostOp value over Baseline for urine KIM-1, NGAL, and cystatin C.	Baseline through Day 3 post-cardiac surgery
Secondary	Number of Subjects With Reduction in Urine Output	Documented AE of sustained reduction in urine output, oliguria, or anuria post-cardiac surgery through Day 5	Baseline through post-cardiac surgery through Day 5
Secondary	Number of Subjects With Acute Kidney Injury (AKI)	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).	Baseline through Day 5 post-cardiac surgery

External Links

•   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