Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of RBT-1 on reducing the risk of post-operative complications in subjects undergoing cardiac surgery on cardiopulmonary bypass (CPB). A sub-study will also be conducted to evaluate the pharmacokinetic (PK) profile of a single administration of RBT-1 by means of a popPK approach in subjects scheduled to undergo cardiac surgery.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery

Conditions
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Post-Operative Complications in Cardiac Surgery

Intervention / Treatment
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* Drug: RBT-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ≥18 years of age at Screening. Planned to undergo non-emergent CABG and/or cardiac valve surgery requiring CPB; non-emergent surgery must allow for study drug infusion ≥24 but ≤48 hours prior to surgery. If female, subjects must use an effective method of birth control or abstain from sexual relations with a male partner (unless has undergone tubal ligation or hysterectomy or is at least 1 year postmenopausal) for the duration of their study participation. If male, subjects must use an effective method of birth control or abstain from sexual relations with a female partner for the duration of their study participation, unless the subject has had a vasectomy ≥6 months prior to infusion with study drug. Willingness to comply with all study-related procedures and assessments. Exclusion Criteria: Surgery planned to occur <24 hours from the start of study drug infusion. Presence of acute organ dysfunction (AKI, acute decompensated heart failure, acute respiratory failure, stroke, etc) as assessed by the Investigator at the time of Screening. Surgery to be performed without CPB. Chronic kidney disease (CKD) requiring dialysis. Hypokalemia and/or hypomagnesemia within 24 hours prior to study drug infusion; electrolytes can be replenished if low. Cardiogenic shock or requirement for inotropes, vasopressors, or other mechanical devices, such as intra-aortic balloon pump (IABP). Known history of cancer within the past 2 years, except for carcinoma in situ of the cervix or breast, early-stage prostate cancer, or adequately treated non-melanoma cancer of the skin. Known or suspected sepsis at time of Screening. Asplenia (anatomic or functional). History of hemochromatosis, iron overload, or porphyria. Known hypersensitivity or previous anaphylaxis to SnPP or FeS. Female subject who is pregnant or breastfeeding. Participation in a study involving an investigational drug or device within 30 days prior to study drug infusion. In the opinion of the Investigator, for any reason, the subject is an unsuitable candidate to receive RBT-1.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized 1:1 to RBT-1 or placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RBT-1<br>Single IV infusion prior to cardiac surgery | Drug: RBT-1<br>* Intravenous administration<br>|
| Placebo Comparator: Placebo<br>Single IV infusion prior to cardiac surgery | Drug: Placebo<br>* Intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hierarchical composite of the following outcomes: death, incidence of AKI requiring dialysis, days in ICU, and 30-day cardiopulmonary readmission | The analysis will be based on a win ratio, which uses the Finkelstein-Schoenfeld method wherein all RBT-1 patients are paired with all placebo patients; each pair is declared to be a win for RBT-1, a win for placebo, or a tie, based on the hierarchical composite. The win ratio is the ratio of the number of wins for RBT-1 divided by the number of wins for placebo. | Index hospitalization (ie, hospitalization post-cardiac surgery up to 60 days) or within 30-days post-discharge, as applicable | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of the Number of Post-operative Complications | The number of the following post-operative complications per patient will be assessed: Death AKI requiring dialysis >3 days in ICU >24 hours on ventilator 30-day cardiopulmonary readmission Need for blood transfusion during index hospitalization New-onset atrial fibrillation during index hospitalization | Index hospitalization (ie, hospitalization post-cardiac surgery up to 60 days) or within 30-days post-discharge, as applicable | 
| ICU Days | Days in ICU | Index hospitalization (ie, hospitalization post-cardiac surgery up to 60 days) | 
| 30-day Cardiopulmonary Readmission Rates | Readmissions due to cardiopulmonary reasons | Within 30-days post-discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Surgery, CABG, Valve, Cardiopulmonary Bypass, Preconditioning