3: PHASE 2 STUDY INTERIM RESULTS OF RBT-1 EFFECT ON POSTOPERATIVE COURSE IN ELECTIVE CABG/VALVE SURGERY

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Introduction: Patients undergoing cardiac surgery are at risk of postoperative complications. RBT-1 is a novel drug with anti-inflammatory and antioxidant activity, which has shown broad organ protective activity in preclinical models. A Phase 2 randomized, double-blind, placebo-controlled study assessed the efficacy of RBT-1, as measured by cytoprotective preconditioning biomarkers, hospital course, and readmission rates. Methods: Eligible subjects undergoing elective coronary artery bypass graft and/or valve surgery on cardiopulmonary bypass were randomized 1:1:1 to receive placebo, low dose RBT-1, or high dose RBT-1 as preconditioning 24-48 hours before surgery. An interim analysis was performed once 60 subjects had completed 30 day follow up. The primary endpoint was to assess the efficacy of RBT-1 in generating a cytoprotective biomarker response. Key secondary/exploratory endpoints included ventilator and ICU days, incidence of acute kidney injury (AKI), hospital length of stay (LOS), and readmission rates. Results: The cytoprotective biomarker composite was significantly increased in response to both RBT-1 dose groups compared to placebo (p < 0.0001). Mean ventilator days in the placebo and combined RBT-1 groups were 3.2 and 1.2, respectively (p=0.03). Mean ICU days in the placebo and RBT-1 groups were 7.0 and 2.7, respectively (p=0.0375). AKI incidence was decreased by 52%, with a 27% and 13% incidence in the placebo and RBT-1 groups, respectively. Mean LOS in the placebo and RBT-1 groups were 10.9 and 8.9 days, respectively, resulting in a 2-day reduction. Hospital readmission at 30 days was reduced by 91%, with rates of 31.8% and 2.6% in the placebo and RBT-1 groups, respectively (p=0.0027). Treatment with RBT-1 was generally well tolerated. The most common treatment-related adverse event was photosensitivity. Conclusions: RBT-1 is a novel drug with cytoprotective preconditioning activity. Interim Phase 2 results suggest RBT-1 protects against postoperative complications of cardiac surgery. The improvements in renal complications, hospital course, and readmission rates are expected given the broad organ protective mechanism of RBT-1. Final results of this study are expected in 2023.