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| Name | Class |
|---|---|
| American Heart Association | OTHER |
| University of Aarhus | OTHER |
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The main purpose of this pilot study is to test the effects of thiamine (vitamin B1) administration before and after major cardiac surgery. Half of patients will receive thiamine and the other half will receive placebo.
The investigators' main hypothesis is that thiamine will improve cellular oxygen consumption and lead to decreased levels of post-operative lactate levels and ultimately improved patient outcomes.
Over 230,000 patients in the United States undergo Coronary Artery Bypass Grafting (CABG) each year. While mortality is relatively low, morbidity remains substantial with a significant risk of prolonged time on mechanical ventilation, prolonged length of hospital and intensive care unit stay and many other complications. CABG causes a profound stress response and significant metabolic alterations occur, including a shift from aerobic to anaerobic metabolism, causing increased levels of pyruvate and lactate. Elevated lactate, a marker of anaerobic metabolism, is a common and significant finding in patients after CABG and is correlated with increased mortality and morbidity.
Aerobic metabolism occurs when pyruvate enters the mitochondria through pyruvate decarboxylation to acetyl-Coenzyme A, facilitated by the enzyme pyruvate dehydrogenase (PDH). Decreased PDH activity may cause a shift toward anaerobic metabolism and play a role in the changes seen in patients undergoing CABG. Thiamine (vitamin B1) is a key co-factor for PDH function and will increase activity even in non-deficient states. The investigators hypothesize that thiamine administration will increase PDH activity in patients undergoing CABG, leading to increased cellular oxygen consumption, as represented by decreased lactate levels after surgery, and ultimately improved clinical outcomes.
In order to test the investigators' hypothesis and to obtain data for a large-scale clinical trial evaluating relevant clinical endpoints, the investigators are conducting a randomized, double-blind, pilot trial of thiamine in high-risk patients undergoing CABG.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Arm | Placebo Comparator | 50 mL normal saline solution |
|
| Thiamine | Experimental | 200 mg thiamine in 50 mL normal saline solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thiamine | Drug | 200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Lactate Levels | Post-surgery within 1 hour of arrival to the ICU |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity | PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method. Reported as relative change from before the surgery. | Post-surgery within 1 hour of arrival to the ICU |
| Measure | Description | Time Frame |
|---|---|---|
| Lactate Levels | Six hours after end of surgery surgery | |
| Pyruvate Dehydrogenase (PDH) Enzyme Activity | PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael W Donnino, M.D. | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27044557 | Derived | Andersen LW, Holmberg MJ, Berg KM, Chase M, Cocchi MN, Sulmonte C, Balkema J, MacDonald M, Montissol S, Senthilnathan V, Liu D, Khabbaz K, Lerner A, Novack V, Liu X, Donnino MW. Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind, placebo-controlled, phase II trial. Crit Care. 2016 Mar 14;20:92. doi: 10.1186/s13054-016-1245-1. |
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206 patients not included for various reasons. 5 patients were randomized, but never received the assigned treatment and was therefore not included in the pre-specified modified intend-to-treat analysis.
275 coronary artery bypass grafting patients screened between January and July 2015
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Arm | 50 mL normal saline solution Normal saline solution: 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) |
| FG001 | Thiamine | 200 mg thiamine in 50 mL normal saline solution Thiamine: 200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Modified intention to treat analysis
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Arm | 50 mL normal saline solution Normal saline solution: 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) |
| BG001 | Thiamine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Lactate Levels | Modified intention to treat | Posted | Median | Inter-Quartile Range | mmol/L | Post-surgery within 1 hour of arrival to the ICU |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Arm | 50 mL normal saline solution Normal saline solution: 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Lars W. Andersen | Beth Israel Deaconess Medical Center | 6173886343 | larswiuffandersen@gmail.com |
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| ID | Term |
|---|---|
| D013831 | Thiamine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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| Normal saline solution | Drug | 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) |
|
| Patients With Post-operative Complications |
Atrial fibrillation, delirium, renal failure, stroke, myocardial infarction, acute respiratory distress syndrome, infection |
| Until hospital discharge, limit 60 days |
| Length of Stay | Duration of intensive care unit stay | Until hospital discharge, limit 60 days |
| Mortality | Until hospital discharge, limit 60 days |
| Six hours after end of surgery surgery |
| Time on Mechanical Ventilation | Limit 60 days |
| Time on Vasopressors | Limit 60 days |
| Global Oxygen Consumption (VO2) | VO2 will be measured with a Compact Anesthesia monitor | From arrival to ICU to extubation, limit 6 hours |
| Cellular Oxygen Consumption | Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzers | Post-surgery within 1 hour of arrival to the ICU |
| Protocol Violation |
|
200 mg thiamine in 50 mL normal saline solution
Thiamine: 200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity | PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method. Reported as relative change from before the surgery. | Posted | Median | Inter-Quartile Range | Percent change from baseline | Post-surgery within 1 hour of arrival to the ICU |
|
|
|
| Secondary | Patients With Post-operative Complications | Atrial fibrillation, delirium, renal failure, stroke, myocardial infarction, acute respiratory distress syndrome, infection | Posted | Number | participants | Until hospital discharge, limit 60 days |
|
|
|
| Secondary | Length of Stay | Duration of intensive care unit stay | Posted | Median | Inter-Quartile Range | days | Until hospital discharge, limit 60 days |
|
|
|
| Secondary | Mortality | Posted | Number | participants | Until hospital discharge, limit 60 days |
|
|
|
| Other Pre-specified | Lactate Levels | Not Posted | Six hours after end of surgery surgery | Participants |
| Other Pre-specified | Pyruvate Dehydrogenase (PDH) Enzyme Activity | PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method | Not Posted | Six hours after end of surgery surgery | Participants |
| Other Pre-specified | Time on Mechanical Ventilation | Not Posted | Limit 60 days | Participants |
| Other Pre-specified | Time on Vasopressors | Not Posted | Limit 60 days | Participants |
| Other Pre-specified | Global Oxygen Consumption (VO2) | VO2 will be measured with a Compact Anesthesia monitor | Not Posted | From arrival to ICU to extubation, limit 6 hours | Participants |
| Other Pre-specified | Cellular Oxygen Consumption | Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzers | Not Posted | Post-surgery within 1 hour of arrival to the ICU | Participants |
| 0 |
| 33 |
| 0 |
| 33 |
| EG001 | Thiamine | 200 mg thiamine in 50 mL normal saline solution Thiamine: 200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) | 0 | 31 | 0 | 31 |
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| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |