Thiamine as a Renal Protective Agent in Septic Shock

Phase 2

Completed

• Conditions: Thiamine Deficiency; Sepsis; Kidney Injury
• Interventions: Drug: Placebo; Drug: Thiamine Hydrochloride

• Registration Number: NCT03550794
• Lead Sponsor: Beth Israel Deaconess Medical Center

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.

Study Timeline

• Study First Submitted: 2018-05-25
• Study First Submitted QC: 2018-06-07
• Study First Posted: 2018-06-08
• Study Start: 2018-09-04
• Primary Completion: 2022-04-05
• Study Completion: 2022-04-05
• Results First Submitted: 2023-05-01
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-02
• Last Update Submitted: 2023-06-02
• Results First Posted: 2023-06-27
• Last Update Posted: 2023-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Thiamine	Thiamine Hydrochloride	200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)

Primary Outcome Measures

Name	Time	Method
Kidney Injury Biomarker	Enrollment to 72-hours	Change in creatinine over time

Secondary Outcome Measures

Name	Time	Method
Number of Participants Receiving Renal Replacement Therapy	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.
Change in Lactate Level	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	Day 3 after enrollment	Number of Participants with Delirium on Day 3 after enrollment
In-hospital Mortality	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
Novel Biomarkers of Renal Injury	24 hours after enrollment	KIM-1, NGAL, Cystatin-C at 24-hours after enrollment
ICU Free Days	From date of enrollment until 28 days after enrollment	Days alive and free of the ICU through day 28
Number of Participants Experiences Acute Renal Failure	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 the Sequential Organ Failure Assessment Score	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.

Trial Locations

Locations (4)

Northshore University Hospital; 🇺🇸 Manhasset, New York, United States

Long Island Jewish Hospital; 🇺🇸 Queens, New York, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Montefiore Medical Center; 🇺🇸 New York, New York, United States