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
• Authors: Andre Lamy; Glenn M. Chertow; Michael Jessen; Alonso Collar; Craig D. Brown; Charles A. Mack; Mohamed Marzouk; Vincent Scavo; T Benton Washburn; David Savage; Julian Smith; Jayme Bennetts; Roland Assi; Christian Shults; Arman Arghami; Javed Butler; P.J. Devereaux; Richard Zager; Chao Wang; Steve Snapinn; Austin Browne; Jeannette Rodriguez; Stacey Ruiz; Bhupinder Singh; Andre Lamy; Glenn Chertow; Michael Jessen; Alonso Collar; Craig Brown; Charles Mack; Mohamed Marzouk; Vincent Scavo; T Benton Washburn; David Savage; Julian Smith; Jayme Bennetts; Roland Assi; Christian Shults; Arman Arghami; Dominic Tedesco; John MacArthur; Jonathan Praetor; Divyakant Gandhi; Joel Corvera; Javed Butler; P.J. Devereaux; Austin Browne; Chao Wang; Steve Snapinn; Richard Zager; Jeannette Rodriguez; Stacey Ruiz; Bhupinder Singh

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.