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Thiamine as a Renal Protective Agent in Septic Shock

Primary Purpose

Sepsis, Kidney Injury, Thiamine Deficiency

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Thiamine Hydrochloride
Placebo
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Beth Israel Deaconess Medical Center
  • Northshore University Hospital
  • Montefiore Medical Center
  • Long Island Jewish Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Thiamine

Placebo

Arm Description

200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)

Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)

Outcomes

Primary Outcome Measures

Kidney Injury Biomarker
Change in creatinine over time

Secondary Outcome Measures

Number of Participants Receiving Renal Replacement Therapy
Number of participants who received renal replacement therapy in thiamine and placebo groups.
ICU Free Days
Days alive and free of the ICU through day 28
In-hospital Mortality
Length of hospital stay truncated at 60 days
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).
Change in Lactate Level
Change in lactate level between enrollment and 72 hours after enrollment
Number of Participants With Delirium on Day 3
Number of Participants with Delirium on 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.
Novel Biomarkers of Renal Injury
KIM-1, NGAL, Cystatin-C at 24-hours after enrollment

Full Information

First Posted
May 25, 2018
Last Updated
June 2, 2023
Sponsor
Beth Israel Deaconess Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03550794
Brief Title
Thiamine as a Renal Protective Agent in Septic Shock
Official Title
Thiamine as a Renal Protective Agent in Septic Shock: A Randomized, Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
September 4, 2018 (Actual)
Primary Completion Date
April 5, 2022 (Actual)
Study Completion Date
April 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Kidney Injury, Thiamine Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
A randomization list will be prepared by an independent statistician using 1:1 randomization in blocks of two and four. This list will be provided to the research pharmacy, and the research pharmacy will be the only unblinded people involved with the study, and will have no patient contact or role in the analysis or other aspects of the study. Thiamine is colorless and odorless, and the 200mg dose is mixed in 5mL of normal saline. Placebo will be 50mL of normal saline and is indistinguishable in appearance from thiamine. Study team, clinical team and patient and family will all be blind to the allocation.
Allocation
Randomized
Enrollment
95 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Thiamine
Arm Type
Experimental
Arm Description
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Intervention Type
Drug
Intervention Name(s)
Thiamine Hydrochloride
Other Intervention Name(s)
Thiamine, Vitamin B1
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline, 0.9%NACL
Intervention Description
50ml of 0.9% NACL will serve as the placebo
Primary Outcome Measure Information:
Title
Kidney Injury Biomarker
Description
Change in creatinine over time
Time Frame
Enrollment to 72-hours
Secondary Outcome Measure Information:
Title
Number of Participants Receiving Renal Replacement Therapy
Description
Number of participants who received renal replacement therapy in thiamine and placebo groups.
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
Title
ICU Free Days
Description
Days alive and free of the ICU through day 28
Time Frame
From date of enrollment until 28 days after enrollment
Title
In-hospital Mortality
Description
Length of hospital stay truncated at 60 days
Time Frame
From date of enrollment until discharge from the hospital or date of death, whichever comes first, up to 60 days after enrollment
Title
Number of Participants Experiences Acute Renal Failure
Description
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).
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
Title
Change in Lactate Level
Description
Change in lactate level between enrollment and 72 hours after enrollment
Time Frame
From time of enrollment until 72 hours after enrollment
Title
Number of Participants With Delirium on Day 3
Description
Number of Participants with Delirium on Day 3 after enrollment
Time Frame
Day 3 after enrollment
Title
Change in the Sequential Organ Failure Assessment Score
Description
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 Frame
Time of enrollment until 72 hours after enrollment
Title
Novel Biomarkers of Renal Injury
Description
KIM-1, NGAL, Cystatin-C at 24-hours after enrollment
Time Frame
24 hours after enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ari Moskowitz, MD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Northshore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Montefiore Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Long Island Jewish Hospital
City
Queens
State/Province
New York
ZIP/Postal Code
11040
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
28207287
Citation
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.
Results Reference
background
PubMed Identifier
26771781
Citation
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.
Results Reference
background

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Thiamine as a Renal Protective Agent in Septic Shock

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