NAD+ Augmentation in Cardiac Surgery Associated Myocardial Injury Trial

Study Overview
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Brief Summary
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A Randomized, Double-blind, placebo-controlled Trial to Evaluate the Efficacy of Oral Nam for the Prevention of Acute Kidney Injury in Patients Undergoing On-Pump Cardiac Surgery

Detailed Description
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This trial is a single-center, randomized, double-blind placebo-controlled Trial of Nam versus placebo in patients undergoing on-pump cardiac surgery. After screening and enrollment, patients will be stratified according to CKD status (eGFR<45 ml/min/m2) and surgical site and randomized in a 1:1 manner to receive either Nam 3 grams or placebo on the day of surgery and post-surgical days one and two. The overall trial duration is planned for 42 months, consisting of 39 months of active recruitment and treatment period and three months of follow-up from the last patient enrolled.

Official Title
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NAD+ Augmentation in Cardiac Surgery Associated Myocardial Injury (NACAM) Trial

Conditions
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Ischemia Reperfusion Injury, Myocardial Injury, Acute Kidney Injury

Intervention / Treatment
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* Drug: Niacinamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Informed consent before any study-related activities. Men or women >18 years of age who are scheduled for non-emergent cardiac surgery procedures requiring CPB and are at increased risk for surgery-related adverse cardiovascular outcomes. Procedures include: CABG Aortic, mitral, tricuspid, or pulmonic valve replacement or repair CABG with aortic, mitral, tricuspid, and/or pulmonic valve replacement Risk factors for surgery related to adverse cardiovascular outcomes include one or more of the following: Valve surgery eGFR < 45 ml/min/1.73m2 Documented LVEF ≤ 35% within six months before surgery Documented history of heart failure Insulin-requiring diabetes Non-insulin-requiring diabetes and the presence of ≥+2 proteinuria on urinalysis (or equivalent on urine protein-to-creatinine ratio or urine albumin-to-creatinine ratio) Preoperative anemia (hemoglobin <11g/dl for men and women) History of prior CABG Age ≥65 Exclusion Criteria Preexisting AKI within seven days before surgery as defined by KDIGO stage ≥1 (serum creatinine-based) Kidney transplant status Off-pump cardiac surgery ESRD Emergent cardiac surgery Pregnancy Patient enrolled in competing research studies that may affect outcomes Patients held in an institution by legal or official order

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral niacinamide<br> | Drug: Niacinamide<br>* Niacinamide 3 grams on the day of surgery and post-surgical days one and two<br>|
| Placebo Comparator: Matched placebo<br> | Drug: Placebo<br>* Matched placebo on the day of surgery and post-surgical days one and two<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin T AUC | Troponin T AUC, composed of single daily serum measurements | From baseline to three days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean difference in uQuin/Tryp ratio AUC | Mean difference in uQuin/Tryp ratio AUC composed of single daily serum measurements | From baseline to three days after surgery | 
| Mean difference in eGFR | Mean difference in eGFR (CKD-EPI formula) | From baseline through day 5. |