Thiamine Supplementation in Patients With Septic Shock

Study Overview
=================
Brief Summary
-----------------
To determine if intravenous thiamine would decrease the time to reversal of shock in patients with septic shock.

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.

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

Conditions
-----------------
Septic Shock, Shock, Septic, Lactic Acidosis, Thiamine Deficiency

Intervention / Treatment
-----------------
* Drug: Thiamine
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thiamine Supplementation Group<br>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<br> <br> * Other names: Vitamin B1;|
| Placebo Comparator: Placebo Group<br>Patients will receive placebo (50mL 5% dextrose) once daily for 7 days or until discharge from the intensive care unit. | Drug: Placebos<br> <br> * 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 |