Thiamine as a Renal Protective Agent in Septic Shock

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on renal function in septic shock.

Detailed Description
-----------------
This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on renal injury in septic shock. Patients admitted with septic shock who have a lactate of at least 2.0mmol/L and do not have pre-existing renal failure requiring dialysis will be eligible for the study. Enrolled patients will be randomized to intravenous thiamine 200mg twice daily for 6 doses or matching placebo. Blood will be drawn at several time points to assess biomarkers of renal injury. Secondary endpoints include need for renal replacement therapy, length of ICU stay, and hospital mortality.

Official Title
-----------------
Thiamine as a Renal Protective Agent in Septic Shock: A Randomized, Controlled Study

Conditions
-----------------
Sepsis, Kidney Injury, Thiamine Deficiency

Intervention / Treatment
-----------------
* Drug: Thiamine Hydrochloride
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult ≥18 years of age Suspected or Confirmed Infection (defined as collection of a blood/fluid culture and provision of an antimicrobial) Receipt of a vasopressor agent (e.g. norepinephrine, phenylephrine, vasopressin) Serum lactate ≥2mmol/L Creatinine >1.0mg/dL Exclusion Criteria: Clinical indication for thiamine administration (alcoholism, known or highly suspected deficiency) or treatment with thiamine beyond the amount found in a standard multivitamin within the last 10 days Renal replacement therapy within the past 30 days Comfort measures only or anticipated withdrawal of support within 24 hours Protected populations (pregnant women, prisoners) Known thiamine allergy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thiamine<br>200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses) | Drug: Thiamine Hydrochloride<br>* Thiamine hydrochloride is a water soluble vitamin (vitamin B1). 200mg of thiamine hydrochloride in 50ml 0.9%NACL will be administered twice daily for 3 days.<br>* Other names: Vitamin B1;|
| Placebo Comparator: Placebo<br>Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations) | Drug: Placebo<br>* 50ml of 0.9% NACL will serve as the placebo<br>* Other names: 0.9%NACL;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney Injury Biomarker | Change in creatinine over time | Enrollment to 72-hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Receiving Renal Replacement Therapy | Number of participants who received renal replacement therapy in thiamine and placebo groups. | From date of enrollment until discharge from the intensive care unit (ICU) or date of death, whichever comes first, up to 60 days after enrollment | 
| ICU Free Days | Days alive and free of the ICU through day 28 | From date of enrollment until 28 days after enrollment | 
| In-hospital Mortality | Length of hospital stay truncated at 60 days | From date of enrollment until discharge from the hospital or date of death, whichever comes first, up to 60 days after enrollment | 
| Number of Participants Experiences Acute Renal Failure | Acute renal failure as defined by the KDIGO (Kidney Disease Improving Global Outcomes) AKI (Acute Kidney Injury) criteria. In brief, a patient can meet these criteria if their serum creatinine increases (for example, serum creatinine increases to 1.5x or higher of baseline serum creatinine, or if it crosses 4mg/dL), or if renal replacement therapy is initiated, or if urine output decreases (for example, <0.5ml/kg/hour for 6-12 hours) or if patient becomes anuric (no urine production). | From date of enrollment until day of discharge from the index ICU admission or date of death, whichever comes first up until 60 days post-enrollment | 
| Change in Lactate Level | Change in lactate level between enrollment and 72 hours after enrollment | From time of enrollment until 72 hours after enrollment | 
| Number of Participants With Delirium on Day 3 | Number of Participants with Delirium on Day 3 after enrollment | Day 3 after enrollment | 
| Change in the Sequential Organ Failure Assessment Score | Change in Sequential Organ Failure Assessment Score (SOFA) score between enrollment and 72 hours after enrollment. SOFA scores are reported on a scale between 0-24, with 0 representing best outcome and 24 representing worst outcome. | Time of enrollment until 72 hours after enrollment | 
| Novel Biomarkers of Renal Injury | KIM-1, NGAL, Cystatin-C at 24-hours after enrollment | 24 hours after enrollment |