Ischemia Reperfusion Injury, Myocardial Injury, Acute Kidney Injury
Conditions
Brief summary
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
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.
Interventions
DRUGNiacinamide
Niacinamide 3 grams on the day of surgery and post-surgical days one and two
DRUGPlacebo
Matched placebo on the day of surgery and post-surgical days one and two
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Beth Israel Deaconess Medical Center
Cedars-Sinai Medical Center
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Troponin T AUC | From baseline to three days after surgery | Troponin T AUC, composed of single daily serum measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean difference in uQuin/Tryp ratio AUC | From baseline to three days after surgery | Mean difference in uQuin/Tryp ratio AUC composed of single daily serum measurements |
| Mean difference in eGFR | From baseline through day 5. | Mean difference in eGFR (CKD-EPI formula) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Perioperative inotropic-score and vasoactive-inotropic score. | At 6, 12, 24, and 48 hours post operatively | • Mean inotropic-score and vasoactive-inotropic score |
| Number of Participants with the following Adverse Events and Serious Adverse Events | From baseline through day 90 | * Postoperative dysrhythmias * Postoperative re-hospitalization. * Heart failure * Surgical wound infection * Transfusion requiring perioperative bleed * Post-surgical deep vein thrombosis and pulmonary emboli * Nosocomial infection * Nausea and vomiting * Adverse events leading to treatment discontinuation * Perioperative liver injury (x2 upper normal-limit) * Post-operative thrombosis and pulmonary emboli * Impairment of renal function (KDIGO AKI) |
| Perioperative brain-natriuretic peptide AUC | From baseline to three days after surgery | BNP AUC, composed of single daily serum measurements |
| Perioperative fluid volume administration. | From baseline through day 2 | • Mean daily perioperative fluid volume administration |
| Length of index hospital stay. | From baseline through day 90 | • Mean length of index hospital stay (days) |
| Length of intensive care unit stay. | From baseline through day 90 | • Mean length of intensive care unit stay (days) |
Countries
United States
Contacts
Primary ContactAli Poyan Mehr, MD
Outcome results
None listed