Thiamine as a Renal Protective Agent in Septic Shock

Overview

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

Full Title of Study: “Thiamine as a Renal Protective Agent in Septic Shock: A Randomized, Controlled Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: April 5, 2022

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.

Interventions

  • Drug: Thiamine Hydrochloride
    • 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.
  • Drug: Placebo
    • 50ml of 0.9% NACL will serve as the placebo

Arms, Groups and Cohorts

  • Experimental: Thiamine
    • 200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
  • Placebo Comparator: Placebo
    • Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)

Clinical Trial Outcome Measures

Primary Measures

  • Kidney Injury Biomarker
    • Time Frame: Enrollment to 72-hours
    • Change in creatinine over time

Secondary Measures

  • Number of Participants Receiving Renal Replacement Therapy
    • Time Frame: 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
    • Number of participants who received renal replacement therapy in thiamine and placebo groups.
  • ICU Free Days
    • Time Frame: From date of enrollment until 28 days after enrollment
    • Days alive and free of the ICU through day 28
  • In-hospital Mortality
    • Time Frame: From date of enrollment until discharge from the hospital or date of death, whichever comes first, up to 60 days after enrollment
    • Length of hospital stay truncated at 60 days
  • Number of Participants Experiences Acute Renal Failure
    • Time Frame: 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
    • 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).
  • Change in Lactate Level
    • Time Frame: From time of enrollment until 72 hours after enrollment
    • Change in lactate level between enrollment and 72 hours after enrollment
  • Number of Participants With Delirium on Day 3
    • Time Frame: Day 3 after enrollment
    • Number of Participants with Delirium on Day 3 after enrollment
  • Change in the Sequential Organ Failure Assessment Score
    • Time Frame: Time of enrollment until 72 hours after enrollment
    • 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.
  • Novel Biomarkers of Renal Injury
    • Time Frame: 24 hours after enrollment
    • KIM-1, NGAL, Cystatin-C at 24-hours after enrollment

Participating in This Clinical Trial

Inclusion Criteria

1. Adult ≥18 years of age 2. Suspected or Confirmed Infection (defined as collection of a blood/fluid culture and provision of an antimicrobial) 3. Receipt of a vasopressor agent (e.g. norepinephrine, phenylephrine, vasopressin) 4. Serum lactate ≥2mmol/L 5. Creatinine >1.0mg/dL Exclusion Criteria:

1. 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 2. Renal replacement therapy within the past 30 days 3. Comfort measures only or anticipated withdrawal of support within 24 hours 4. Protected populations (pregnant women, prisoners) 5. Known thiamine allergy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Beth Israel Deaconess Medical Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Michael Donnino, Associate Professor of Emergency Medicine – Beth Israel Deaconess Medical Center
  • Overall Official(s)
    • Ari Moskowitz, MD, Principal Investigator, Beth Israel Deaconess Medical Center

References

Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial. Ann Am Thorac Soc. 2017 May;14(5):737-741. doi: 10.1513/AnnalsATS.201608-656BC.

Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572.

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