Design of START: A Phase 2 Study Evaluating the Safety and Efficacy of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing Cardiac Surgery
AKI Clinical, Outcomes, and Trials - 1
102 AKI: Clinical, Outcomes, and Trials
Singh, Bhupinder, University of California Irvine, University of California Irvine, Irvine, CA, US, Department of Medicine, Irvine, California, United States
Bhupinder Singh,
Lavin, Philip T., Boston Biostatistics Research Foundation, Framingham, Massachusetts, United States
Philip T. Lavin,
Orfanos, Andreas, Montreal Health Innovations Coordinating Center, Montreal, Quebec, Canada
Andreas Orfanos,
Ruiz, Stacey, Renibus Therapeutics, Southlake, Texas, United States
Stacey Ruiz,
Keyser, Donald Jeffrey, Renibus Therapeutics, Southlake, Texas, United States
Donald Jeffrey Keyser,
Guillem, Alvaro F., Renibus Therapeutics, Southlake, Texas, United States
Alvaro F. Guillem,
Zager, Richard A., Fred Hutchinson Cancer Research Center, Seattle, Washington, United States
Richard A. Zager,
Tangri, Navdeep, University of Manitoba, University of Manitoba, Winnipeg, MB, CA, Winnipeg, Manitoba, Canada
Navdeep Tangri,
Tardif, Jean-Claude, Institut De Cardiologie de Montreal, Montreal, Quebec, Canada
Jean-Claude Tardif,
Cardiac surgery is associated with an increased risk of acute kidney injury (AKI). RBT-1 induces non-ischemic tissue preconditioning that has shown organ protective effects in several animal models of AKI. Markers of cytoprotection observed with RBT-1 treatment in animals were also found to be upregulated in a Phase 1 study of RBT-1 in healthy volunteers and subjects with Stages 3 and 4 chronic kidney disease (CKD). Based on these data, we have designed a Phase 2, placebo-controlled, double-blind, randomized, multicenter study that will assess the effect of RBT-1 on preconditioning response biomarkers in subjects scheduled to undergo cardiac surgery
This study will enroll 126 subjects scheduled to undergo coronary artery bypass graft (CABG) and/or cardiac valve surgery. Eligible subjects will be randomized to receive a single dose of RBT-1 or placebo via intravenous infusion between 24 and 48 hours prior to scheduled cardiac surgery. Subjects will be followed through Day 90.
Inclusion/Exclusion Criteria:
Subjects eligible for enrollment include adults who are scheduled to undergo non-emergent, on-pump coronary artery and/or cardiac valve surgery. Major exclusion criteria include CKD with eGFR ≤20 ml/min/1.73m2 or need for dialysis.
The primary objective of this study is to evaluate the efficacy of RBT-1 on preconditioning response biomarkers from baseline through Day 3 post-cardiac surgery. Based on preclinical data, plasma heme oxygenase-1 [HO-1], ferritin, and interleukin-10 [IL-10]) have been identified as the relevant biomarkers for this study. Secondary objectives include change in tubular injury biomarkers and incidence of AKI based on KDIGO classification. Exploratory objectives include the occurrence of major adverse kidney events (MAKE) through Days 30 and 90.
The multinational START study will assess the cytoprotective preconditioning response to RBT-1 in subjects undergoing cardiac surgery.