The majority of patients undergoing cardiac surgery, especially those on cardiopulmonary bypass (CPB), experience post-operative complications such as new-onset atrial fibrillation (POAF) and acute kidney injury (AKI), largely driven by oxidative stress and inflammation.
Several approaches have been explored to reduce complications following cardiac surgery, however, a clinically meaningful impact has yet to be realized.
- Remote ischemic preconditioning failed to demonstrate consistent benefit in clinical trials due to challenges in determining and delivering an ‘effective and safe dose’ of ischemia.
- Pharmacologic preconditioning, administering agents such as methylprednisolone, deferoxamine, or dexmedetomidine before surgery, has also been explored without significant benefit.
RBT-1 is an investigational agent that activates antioxidant and anti-inflammatory pathways. In a Phase 2 randomized, placebo-controlled study in patients undergoing CABG and/or valve surgery on CPB, RBT-1 administered 1-2 days prior to surgery resulted in:
- A significant increase in cytoprotective preconditioning biomarkers.
- A numeric reduction in the occurrence of post-operative complications, including ventilator time; ICU and hospital days; 30-day readmission rates; AKI and POAF incidence.
- A generally well tolerated safety profile with the most frequent adverse event related to RBT-1 being mild-to-moderate, transient photosensitivity, not requiring therapeutic intervention.
RBT-1 received Fast Track and Breakthrough Therapy designation by the US FDA and advanced to a Phase 3 clinical study (PROTECT), which recently completed enrollment.
- Primary study objective is to evaluate the efficacy of RBT-1 compared with placebo on a hierarchical composite (win ratio) consisting of death, AKI requiring dialysis, 30-day cardiopulmonary readmission, and ICU days.
- Secondary objectives include the number of post-operative complications, 30-day cardiopulmonary readmission rates, and ICU days.
- Results are expected in the second half of 2025
The Takeaway
Complications following cardiac surgery are often driven by oxidative stress and inflammation. An investigational preconditioning drug, RBT-1, is being developed to prevent post-operative complications in patients undergoing CABG and/or valve surgery on CPB by activating intrinsic antioxidant and anti-inflammatory pathways prior to surgery. Results of the pivotal Phase 3 study are expected in the second half of 2025 and aim to provide confirmatory evidence on the potential of RBT-1 to significantly improve clinical outcomes for patients undergoing cardiac surgery.
