## Protocol Section
### Identification Module
**NCT ID:** NCT01462279

**Acronym:** VO2

**Brief Title:** Effect of Thiamine on Oxygen Utilization (VO2) in Critical Illness

**Official Title:** The Effect of Thiamine on VO2 Levels in Critically Ill Patients

#### Organization Study ID Info
**ID:** 2010P000312
#### Organization
**Class:** OTHER
**Full Name:** Beth Israel Deaconess Medical Center
### Status Module
#### Completion Date
**Date:** 2012-10

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-01-16

**Type:** ACTUAL

**Last Update Submit Date:** 2017-12-11

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2012-10

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2016-11-30

**Type:** ESTIMATED

**Results First Submit Date:** 2016-10-07

**Results First Submit QC Date:** 2016-10-07

#### Start Date
**Date:** 2011-09

**Status Verified Date:** 2017-12

#### Study First Post Date
**Date:** 2011-10-31
**Type:** ESTIMATED
**Study First Submit Date:** 2011-10-25
**Study First Submit QC Date:** 2011-10-27
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** American Medical Association

#### Lead Sponsor

**Class:** OTHER

**Name:** Beth Israel Deaconess Medical Center

#### Responsible Party

**Investigator Affiliation:** Beth Israel Deaconess Medical Center

**Investigator Full Name:** Michael Donnino

**Investigator Title:** Associate Professor of Emergency Medicine

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The objective of this study is to determine the effect of thiamine therapy on oxygen consumption in critically-ill patients. The investigators will evaluate this by measuring VO2 before and after thiamine administration in patients admitted to the ICU and requiring mechanical ventilation.

**Detailed Description:** Extensive research has been done over the past two decades looking at the role of oxygen delivery (DO2) and oxygen utilization (VO2) in critical illness. VO2 depends on cardiac output, arterial oxygen content, and the body's ability to extract oxygen effectively from the blood. Oxygen demand rises in critical illness as the body goes into a catabolic state, and lower VO2 has been associated with higher lactate levels and with poorer outcomes. Although increasing DO2 will often raise VO2, Hayes et al found that a subset of critically-ill patients failed to demonstrate a rise in VO2 in spite of achieving supranormal values of cardiac index (CI) and DO2. This group, in contrast to patients whose VO2 rose with the increase in CI and DO2, had exceedingly poor outcomes, suggesting that an inability to extract oxygen from the blood confers a poorer prognosis.(1)

Thiamine deficiency can manifest in several ways, but the syndrome of wet beriberi, caused by thiamine deficiency, includes lactic acidosis, cardiac decompensation and vasodilatory shock, similar to sepsis and other forms of critical illness. The mechanism by which thiamine deficiency causes dysfunction rests upon the vitamin's essential role in the Krebs cycle and Pentose Phosphate Pathway. Lack of adequate thiamine results in the failure of pyruvate to enter the Krebs Cycle, thus preventing aerobic metabolism. The resulting decrease in aerobic metabolism and increase in anaerobic metabolism leads to decreased oxygen consumption by the tissues and increased lactic acid production. The investigators group has found previously that upwards of 20% of critically ill patients with sepsis are thiamine deficient within 72 hours of presentation. In a dog model of septic shock, Lindenbaum et al have shown that, regardless of thiamine levels, supplementation with thiamine improved not only lactate clearance and mean arterial pressure, but increased VO2 as well. The effect of thiamine on VO2 in critically ill humans has not yet been reported, but an increase in VO2 max after administration of thiamine to healthy volunteers has been described. VO2 is known to rise in inflammatory states, reflecting increased energy expenditure. Prior studies have shown that VO2 will decrease with interventions such as fever control. In spite of VO2 being higher than normal in critically-ill patients, however, the end-organ damage and lactic acidosis suggest that it is not high enough to meet the metabolic demands of the critically-ill body. If the investigators were able to increase VO2 further in critically-ill patients, the investigators could potentially help maintain aerobic metabolism and decrease tissue hypoxia and the resulting end-organ damage. The investigators hypothesis is that administering thiamine intravenously to critically-ill patients will increase VO2.

Multiple methods of measuring VO2 have been used in the ICU, but in the current era where invasive monitoring with routine use of PA catheters is no longer the norm, indirect calorimetry became, for a time, the gold standard for measurement of gas exchange in critically ill, mechanically ventilated patients.(2) The metabolic cart used for indirect calorimetry is cumbersome and requires frequent calibration to maintain accuracy, however, and a newer, more portable method has been designed. The Datex-Ohmeda M-COVX device has been approved for the measurement of VO2 and VCO2 in mechanically ventilated patients. In studies, it has been validated as a method that is as accurate as indirect calorimetry, and perhaps even more accurate at higher FiO2.(3,4) The Datex-Ohmeda M-COVX connects to the Carescape B650 monitor made by GE, and measures VO2 through a single-use spirometer that attaches to the patient's ventilator tubing. In the following proposal, the investigators present a plan to examine the effect of thiamine therapy on VO2 in 30 critically-ill, mechanically ventilated patients, using the Datex-Ohmeda M-COVX module to measure VO2 before and after thiamine administration.

### Conditions Module

**Conditions:**

- Acute Respiratory Failure

**Keywords:**

- acute respiratory failure

- thiamine

- oxygen consumption

- VO2

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Open label - 200mg IV

**Intervention Names:**

- Drug: Thiamine

**Label:** Thiamine

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Thiamine

**Description:** 200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once

**Name:** Thiamine

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** VO2 measurements are taken at baseline and VO2 is continuously monitored over 9 hours. Thiamine is administered three hours after baseline measurements are taken.

**Measure:** Improvement in VO2

**Time Frame:** Baseline to 9 Hours

#### Secondary Outcomes

**Description:** Hemodynamics were collected in all patients but we did not evaluate change in hemodynamics over the 9 hour protocol of the study. Due to the single-arm nature and small size of the study, and with no comparison arm, we did not think we had the statistical power to evaluate for a change in hemodynamics so this was not a planned outcome and was entered in error.

**Measure:** Improvement in Hemodynamics

**Time Frame:** Baseline to Nine Hours

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Adult patients (age \> 18 years) admitted to an ICU
* Mechanically ventilated

Exclusion Criteria:

* Unstable ventilator settings during measurement of VO2
* Temp \> 100 at time of VO2 measurement
* FIO2 \> 60%
* Endotracheal cuff leak, chest tube, or other evident source of air leak
* Thiamine supplementation within 24 hours prior to study enrollment

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Boston

**Country:** United States

**Facility:** Beth Israel Deaconess Medical Center (BIDMC)

**State:** Massachusetts

**Zip:** 02115

#### Overall Officials

**Official 1:**

**Affiliation:** Beth Israel Deaconess Medical Center

**Name:** Katherine M Berg, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Beth Israel Deaconess Medical Center

**Name:** Michael W Donnino, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Berg KM, Gautam S, Salciccioli JD, Giberson T, Saindon B, Donnino MW. Intravenous thiamine is associated with increased oxygen consumption in critically ill patients with preserved cardiac index. Ann Am Thorac Soc. 2014 Dec;11(10):1597-601. doi: 10.1513/AnnalsATS.201406-259BC.

**PMID:** 25390455

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012120

- Term: Respiration Disorders

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14968

- Name: Respiratory Insufficiency

- Relevance: HIGH

- As Found: Respiratory Failure

- ID: M19010

- Name: Critical Illness

- Relevance: LOW

- As Found: Unknown

- ID: M14957

- Name: Respiration Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012131

- Term: Respiratory Insufficiency

### Intervention Browse Module - Ancestors

- ID: D000014803

- Term: Vitamin B Complex

- ID: D000014815

- Term: Vitamins

- ID: D000018977

- Term: Micronutrients

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M16595

- Name: Thiamine

- Relevance: HIGH

- As Found: Patient-controlled analgesia

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M21009

- Name: Micronutrients

- Relevance: LOW

- As Found: Unknown

- ID: M16885

- Name: Trace Elements

- Relevance: LOW

- As Found: Unknown

- ID: T464

- Name: Thiamin

- Relevance: HIGH

- As Found: Patient-controlled analgesia

- ID: T465

- Name: Thiamine

- Relevance: HIGH

- As Found: Patient-controlled analgesia

- ID: T469

- Name: Vitamin B1

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000013831

- Term: Thiamine

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Thiamine

**Description:** Open label - 200mg IV

Thiamine: 200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once

**ID:** EG000

**Other Num at Risk:** 17

**Serious Number At Risk:** 17

**Title:** Thiamine

**Frequency Threshold:** 0

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 17

**Units:** Participants

### Group

**ID:** BG000

**Title:** Thiamine

**Description:** Open label - 200mg IV

Thiamine: 200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 17

**Value:** 66

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 6

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 11

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 16

**Category Title:** Not Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 15

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 17

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Ethnicity (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 5
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** mdonnino@bidmc.harvard.edu
**Organization:** Beth Israel Deaconess Medical Center
**Phone:** 6177542341
**Title:** Dr. Michael W. Donnino
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 8.6
- **Upper Limit:** 
- **Value:** 16.9
**Title:** 
#### Outcome Measure 2
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** VO2 measurements are taken at baseline and VO2 is continuously monitored over 9 hours. Thiamine is administered three hours after baseline measurements are taken.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** Baseline to 9 Hours
**Title:** Improvement in VO2
**Type:** PRIMARY
**Unit of Measure:** ml/min
##### Group
**Description:** Open label - 200mg IV

Thiamine: 200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once
**ID:** OG000
**Title:** Thiamine
#### Outcome Measure 2
**Description:** Hemodynamics were collected in all patients but we did not evaluate change in hemodynamics over the 9 hour protocol of the study. Due to the single-arm nature and small size of the study, and with no comparison arm, we did not think we had the statistical power to evaluate for a change in hemodynamics so this was not a planned outcome and was entered in error.
**Population Description:** Due to the single-arm nature and small size of the study, and with no comparison arm, we did not think we had the statistical power to evaluate for a change in hemodynamics so this was not a planned outcome and was entered in error.
**Reporting Status:** POSTED
**Time Frame:** Baseline to Nine Hours
**Title:** Improvement in Hemodynamics
**Type:** SECONDARY
##### Group
**Description:** Open label - 200mg IV

Thiamine: 200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once
**ID:** OG000
**Title:** Thiamine
### Participant Flow Module
#### Group
**Description:** Open label - 200mg IV

Thiamine: 200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once
**ID:** FG000
**Title:** Thiamine
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 20
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 17
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 3
**Has Results:** True