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

DOI: 10.1016/j.eclinm.2023.102364 Publication Date: 2024-01-08T23:30:22Z
ABSTRACT
BackgroundRBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits preconditioning response through activation antioxidant, anti-inflammatory, iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely effectively elicit in patients undergoing cardiac surgery.MethodsThis phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted 19 centres across the USA, Canada, Australia, enrolled scheduled undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve with cardiopulmonary bypass. Patients were randomised (1:1:1) receive either single intravenous infusion high-dose (90 mg SnPP/240 FeS), low-dose (45 or placebo within 24–48 h surgery. The outcome preoperative response, composite plasma HO-1, IL-10, ferritin. Safety assessed adverse events laboratory parameters. Prespecified criteria permitted early stopping enrichment. This trial registered ClinicalTrials.gov, NCT04564833.FindingsBetween Aug 4, 2021, Nov 9, 2022, 135 who randomly allocated study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) included analysis 42 placebo). At interim, proceeded full enrollment without led greater than did at (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91–4.41; p < 0.0001) (GLSM 2.62; 2.11–3.24; 0.0001). generally well tolerated patients. drug-related event dose-dependent photosensitivity, observed 12 (26%) 46 treated six (13%) (safety population).InterpretationRBT-1 demonstrated statistically significant cytoprotective manageable safety profile. Further research needed. A 3 planned.FundingRenibus Therapeutics, Inc.
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