Thiamine as a Renal Protective Agent in Septic Shock

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

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

Study Overview

• Status: Completed
• Conditions: Sepsis; Kidney Injury; Thiamine Deficiency
• Intervention / Treatment: Drug: Placebo; Drug: Thiamine Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • New York
    • Manhasset, New York, United States, 11030
      • Northshore University Hospital
    • New York, New York, United States, 10467
      • Montefiore Medical Center
    • Queens, New York, United States, 11040
      • Long Island Jewish Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thiamine; 200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)	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.; Other Names: Vitamin B1; Thiamine
Placebo Comparator: Placebo; Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)	Drug: Placebo; 50ml of 0.9% NACL will serve as the placebo; Other Names: Normal Saline; 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
ICU Free Days	Days alive and free of the ICU through day 28	From date of enrollment until 28 days after enrollment
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
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

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Ari Moskowitz, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2018
• Primary Completion (Actual): April 5, 2022
• Study Completion (Actual): April 5, 2022

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 8, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Thiamine Deficiency; Beriberi; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: 2018P-000204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No