Thiamine as a Metabolic Resuscitator in Septic Shock

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01070810
• Collaborator: National Institutes of Health (NIH) (NIH), National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 88
• Location: 1
• Arms: 2
• Duration (Months): 57
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The major goal of this project is to determine whether the use of thiamine in patients with septic shock will result in attenuation of lactic acidosis and a more rapid reversal of shock.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock	Drug: D5W; Drug: Thiamine	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Thiamine as a Metabolic Resuscitator in Septic Shock
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 50 ml D5W	Drug: D5W; Dextrose 5%
Experimental: 2 200mg Thiamine in 50ml D5W	Drug: Thiamine; Thiamine 200mg in 50ml D5W

Outcome Measures

Primary Outcome Measures

1. Lactate Level 24 Hours After the First Study Medication Dose [24 hours]

Secondary Outcome Measures

1. Number of Participants With Shock Reversal [Hospital stay, average 2 weeks]

   Shock reversal was defined as > 24 hours off all vasopressors

2. APACHE II Score at 24 Hours [24 hours]

   APACHE II ("Acute Physiology and Chronic Health Evaluation II") is a severity-of-disease classification system; an integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death

Other Outcome Measures

1. Lactate Level at 24 Hours in Patients With Baseline Thiamine Deficiency [24 hours]

   Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L

2. Number of Participants Dying Before Hospital Discharge in Patients With Baseline Thiamine Deficiency [Hospital stay, average 2 weeks]

   Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Greater than 18 years old

• Suspected or confirmed source of infection

• Hypotension (systolic pressure <90 mmHg) after a minimum 2 liter fluid bolus followed by vasopressor-dependence.

• Lactic Acidosis > 3 mmol/dl

Exclusion Criteria:

• Competing cause of lactic acidosis including: seizures within 3 hours of enrollment, use of linazolid metformin or anti-retrovirals at the time of enrollment, carbon monoxide or cyanide poisoning, highly suspected or known ischemic bowel, and known mitochondrial disorders

• Liver dysfunction specifically defined as AST or ALT elevation greater than 240

• Current Thiamine supplements or usage

• Competing indication for thiamine administration

• Cardiac Arrest

• DNR/DNI or comfort care status (DNR status in an intubated patient receiving full care is eligible)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• National Institutes of Health (NIH)
• National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Michael W Donnino, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Donnino, Michael W. Donnino, MD, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01070810
• Other Study ID Numbers: 2008P000053
• First Posted: Feb 18, 2010
• Last Update Posted: May 15, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Michael Donnino, Michael W. Donnino, MD, Beth Israel Deaconess Medical Center: Septic Shock; Sepsis
• Additional relevant MeSH terms: Shock, Septic; Shock; Thiamine

Study Results

Participant Flow

Arm/Group Title	Placebo	Thiamine
Arm/Group Description	50 ml D5W D5W: Dextrose 5%	200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5%
Period Title: Overall Study
STARTED	45	43
COMPLETED	45	43
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Thiamine	Total
Arm/Group Description	50 ml D5W D5W: Dextrose 5%	200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5%	Total of all reporting groups
Overall Participants	45	43	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (17)	70 (14)	67 (16)
Sex: Female, Male (Count of Participants)
Female	19 42.2%	17 39.5%	36 40.9%
Male	26 57.8%	26 60.5%	52 59.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 4.4%	1 2.3%	3 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 6.7%	4 9.3%	7 8%
White	40 88.9%	36 83.7%	76 86.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 4.7%	2 2.3%
Region of Enrollment (participants) [Number]
United States	45 100%	43 100%	88 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29 (7)	29 (9)	29 (8)

Outcome Measures

1. Primary Outcome

Title	Lactate Level 24 Hours After the First Study Medication Dose
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Thiamine
Arm/Group Description	50 ml D5W D5W: Dextrose 5%	200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5%
Measure Participants	45	43
Median (Inter-Quartile Range) [mmol/L]	2.6	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Thiamine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Number of Participants With Shock Reversal
Description	Shock reversal was defined as > 24 hours off all vasopressors
Time Frame	Hospital stay, average 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Thiamine
Arm/Group Description	50 ml D5W D5W: Dextrose 5%	200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5%
Measure Participants	45	43
Count of Participants [Participants]	32 71.1%	32 74.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Thiamine
	Comments	Time to shock reversal was complicated by a high incidence of death prior to the event. To account for this we classified death as a competing risk event and used the estimated cumulative incidence function (CIF) to illustrate the comparison of CIFs between the two treatment groups using the Fine-Gray competing risk model. We tested the subdistribution hazards of these two CIF functions and obtained the estimated hazard ratio with 95% confidence intervals.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	APACHE II Score at 24 Hours
Description	APACHE II ("Acute Physiology and Chronic Health Evaluation II") is a severity-of-disease classification system; an integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

APACHE II was not available on 6 patients in each group at 24 hour mostly because of early death.

Arm/Group Title	Placebo	Thiamine
Arm/Group Description	50 ml D5W D5W: Dextrose 5%	200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5%
Measure Participants	39	37
Mean (Standard Deviation) [units on a scale]	26 (10)	23 (8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Thiamine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	t-test, 2 sided
	Comments

4. Other Pre-specified Outcome

Title	Lactate Level at 24 Hours in Patients With Baseline Thiamine Deficiency
Description	Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thiamine Deficient Received Thiamine	Thiamine Deficient, Received Placebo
Arm/Group Description	Thiamine deficient (≤ 7 nmol/L) received 200mg Thiamine in 50ml D5W	Thiamine deficient (≤ 7 nmol/L) received 50ml D5W
Measure Participants	15	13
Median (Inter-Quartile Range) [nmol/L]	2.1	3.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Thiamine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Other Pre-specified Outcome

Title	Number of Participants Dying Before Hospital Discharge in Patients With Baseline Thiamine Deficiency
Description	Baseline thiamine deficiency was defined as a baseline thiamine level of ≤ 7 nmol/L
Time Frame	Hospital stay, average 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thiamine Deficient Received Thiamine	Thiamine Deficient, Received Placebo
Arm/Group Description	Thiamine deficient (≤ 7 nmol/L) received 200mg Thiamine in 50ml D5W	Thiamine deficient (≤ 7 nmol/L) received 50ml D5W
Measure Participants	15	13
Count of Participants [Participants]	2 4.4%	6 14%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Thiamine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	Hospital stay, average 2 weeks
Arm/Group Title	Placebo		Thiamine
Arm/Group Description	50 ml D5W D5W: Dextrose 5%		200mg Thiamine in 50ml D5W Thiamine: Thiamine 200mg in 50ml Dextrose 5%
All Cause Mortality
	Placebo		Thiamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/45 (42.2%)		19/43 (44.2%)
Serious Adverse Events
	Placebo		Thiamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Thiamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/43 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.