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

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

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

Study Overview

• Status: Recruiting
• Conditions: Myocardial Injury; Acute Kidney Injury; Ischemia Reperfusion Injury
• Intervention / Treatment: Drug: Niacinamide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 304
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ali Poyan Mehr, MD; Phone Number: 4152644750; Email: ali.x.poyanmehr@kp.org

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • Recruiting
      • Kaiser Permanente San Francisco Medical Center
      • Contact: Ali Poyan Mehr, MD
      • Sub-Investigator: Andrew Avins, MD
      • Sub-Investigator: Lance Rtherford, MD
      • Sub-Investigator: Paul LaPunzina, MD
      • Sub-Investigator: Ahmad Sheikh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with the following Adverse Events and Serious Adverse Events	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)	From baseline through day 90
Length of index hospital stay.	• Mean length of index hospital stay (days)	From baseline through day 90
Length of intensive care unit stay.	• Mean length of intensive care unit stay (days)	From baseline through day 90
Perioperative inotropic-score and vasoactive-inotropic score.	• Mean inotropic-score and vasoactive-inotropic score	At 6, 12, 24, and 48 hours post operatively
Perioperative fluid volume administration.	• Mean daily perioperative fluid volume administration	From baseline through day 2
Perioperative brain-natriuretic peptide AUC	BNP AUC, composed of single daily serum measurements	From baseline to three days after surgery

Collaborators and Investigators

• Sponsor: Kaiser Permanente
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Beth Israel Deaconess Medical Center; Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Postoperative Complications; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Ischemia; Wounds and Injuries; Acute Kidney Injury; Reperfusion Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 1620125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No