Thiamine Supplementation in Patients With Septic Shock

Thiamine Supplementation in Patients With Septic Shock: A Randomized, Double Blind, Placebo Controlled Trial

To determine if intravenous thiamine would decrease the time to reversal of shock in patients with septic shock.

Study Overview

• Status: Withdrawn
• Conditions: Septic Shock; Shock, Septic; Lactic Acidosis; Thiamine Deficiency
• Intervention / Treatment: Drug: Placebos; Drug: Thiamine

Detailed Description

Patients will be randomized to thiamine supplementation or placebo in a 1:1 ratio. Randomization will be done by the hospital pharmacy department whom will be the only unblinded participants. Patients will receive 200mg thiamine in 50mL of 5% dextrose or matching placebo (50mL 5% dextrose) once daily for 7 days or until discharge from the intensive care unit. The drug will be mixed by the pharmacy. Administration will be done in the patients room in the intensive care unit by the patient's assigned nurse. Blood will be collected on admission to the hospital in order to determine baseline lactate level and study eligibility. The measurement of lactate is standard of care in patients with sepsis. Thiamine level will be collected upon enrollment into the study. The ICU nurse or emergency room nurse taking care of the patient at the time of enrollment will draw the blood sample. Standard procedure for measuring thiamine levels will be maintained including protecting the blood sample from light and keeping it on ice while it is delivered to the lab. Serum lactate will be measured daily for 7 days or until discharge from the intensive care unit. The serial measurement of serum lactate is considered standard of care in patients with sepsis.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age>18
• Sepsis (defined as presence of two or more SIRS criteria with documented or suspected infection)
• SIRS: Systemic Inflammatory Response Syndrome (SIRS) is the occurrence of at least two of the following criteria: temperature >38.0ºC or <36.0ºC, heart rate >90 beats/minute, respiratory rate >20 breaths/minute, white blood cell count >12,000 or <4000.
• Lactate >3mmol/L at the time of consent and randomization
• Hypotension (systolic blood pressure <90mmHg) after a >2L fluid bolus
• Vasopressor dependence (defined as the continuous infusion of norepinephrine, dopamine, phenylephrine, vasopressin or epinephrine.)

Exclusion Criteria:

• Known cirrhosis or chronic liver disease
• Current thiamine supplementation
• Clinical indication for thiamine (e.g. Alcohol abuse)
• Comfort measures only designation
• Inability to provide consent
• Other causes for lactate elevation (seizure, use of medications that can cause lactic acidosis such as metformin, linezolid and anti-retrovirals, carbon monoxide, known or suspected bowel or limb ischemia, cardiac arrest prior to enrollment)

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 Supplementation Group; Patients will receive 200mg thiamine in 50mL of 5% dextrose once daily for 7 days or until discharge from the intensive care unit.	Drug: Thiamine; Other Names: Vitamin B1
Placebo Comparator: Placebo Group; Patients will receive placebo (50mL 5% dextrose) once daily for 7 days or until discharge from the intensive care unit.	Drug: Placebos; Other Names: 50mL 5% dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reversal of Shock	Number of hours that the patient required vasopressors	7 days
Time to Normalization of Lactic Acidosis		7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Mortality	Death occurring during the ICU stay	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
ICU Length of Stay	Number of days that the patient remains in the ICU after admission to the ICU	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Jinesh Mehta, MD, Cleveland Clinic Florida

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2016
• Primary Completion (Anticipated): March 14, 2019
• Study Completion (Anticipated): March 14, 2019

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: April 18, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: March 14, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Nutrition Disorders; Sepsis; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Acid-Base Imbalance; Shock, Septic; Shock; Acidosis; Acidosis, Lactic; Thiamine Deficiency; Beriberi; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: FLA 16-058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No