Thiamine as a Renal Protective Agent in Septic Shock

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03550794
• Other study ID #: 2018P-000204
• Status: Completed
• Phase: Phase 2
• Start date: September 4, 2018
• Est. completion date: April 5, 2022

Study information

• Verified date: June 2023
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: April 5, 2022
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Beriberi
• Kidney Injury
• Sepsis
• Thiamine Deficiency

Intervention

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.
• Placebo
50ml of 0.9% NACL will serve as the placebo

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Northshore University Hospital	Manhasset	New York
United States	Montefiore Medical Center	New York	New York
United States	Long Island Jewish Hospital	Queens	New York

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kidney Injury Biomarker	Change in creatinine over time	Enrollment to 72-hours
Secondary	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
Secondary	ICU Free Days	Days alive and free of the ICU through day 28	From date of enrollment until 28 days after enrollment
Secondary	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
Secondary	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
Secondary	Change in Lactate Level	Change in lactate level between enrollment and 72 hours after enrollment	From time of enrollment until 72 hours after enrollment
Secondary	Number of Participants With Delirium on Day 3	Number of Participants with Delirium on Day 3 after enrollment	Day 3 after enrollment
Secondary	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
Secondary	Novel Biomarkers of Renal Injury	KIM-1, NGAL, Cystatin-C at 24-hours after enrollment	24 hours after enrollment