Does High-dose Vitamin B3 Supplementation Prevent Major Adverse Kidney Events During Septic Shock?

Study Overview
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Brief Summary
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Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients and is associated with a high mortality rate. Currently there is no available specific treatment to prevent or treat AKI in this setting. Many experimental and clinical data suggest that Nicotinamide, a safe and inexpensive vitamin, could be effective to prevent major adverse kidney events during septic shock. The main objective of the study is to show the superiority of Nicotinamide supplementation compared to the placebo group, in patients with septic shock admitted to intensive care. A 15% reduction in the incidence of major renal adverse events at day 30 is expected in the Nicotinamide group.

Official Title
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Does High-dose Vitamin B3 Supplementation Prevent Major Adverse Kidney Events During Septic Shock? A Multicenter Randomized Controlled Study

Conditions
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Mortality, Septic Shock, Nicotinamide, Acute Kidney Injury

Intervention / Treatment
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* Drug: Nicotinamide treatment
* Drug: placebo treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with septic shock defined as sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation. Written informed consent Exclusion Criteria: Presence of inclusion criteria for more than 24 hours Immediate indication to start renal replacement therapy at the time of randomization: Hyperkalemia≥ 6.5 mmol /l, metabolic acidosis with pH <7.15 not controlled by medical treatment, diuretic resistant acute pulmonary edema or accumulation of a toxic requiring dialysis. Formal indication of Nicotinamide supplementation according to the attending physician (eg pellagra, undernutrition, severe alcoholism) Known severe chronic kidney disease (clearance <30 ml /min) in the last 3 months preceding the setic shock or kidney transplant recipient. Moribund patient (estimated survival less than 24 hours) Patient who are not expected to survive to day 30 due to terminal-stage disease (terminal respiratory or heart failure, Child C cirrhosis, uncontrolled cancer) Resuscitated cardiac arrest Pregnant or lactating Legal tutorship and guardianship Lack of social security coverage.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin B3<br> | Drug: Nicotinamide treatment<br>* Nicotinamide (500 mg) will be mixed in 50 ml of 0.9% saline and administered intravenously every 12 h for a total of 72 h.<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo treatment<br>* For the placebo group, an identical volume of 0.9% saline will be administered in the same manner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients meeting one or more criteria for MAKE30 | MAKE30 is : in-hospital mortality, receipt of new RRT, or persistent renal dysfunction defined as a final inpatient serum creatinine value ≥2 time baseline serum creatinine | 3 years after study start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Kidney Injury, Septic Shock, Nicotinamide