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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23HL128814-01A1 | U.S. NIH Grant/Contract | View source |
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Study stopped early after consultation with DSMB
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This study is to evaluate whether thiamine can increase oxygen consumption and lower lactate in patients who initially survive an in-hospital cardiac arrest. Patients who are successfully resuscitated after an in-hospital cardiac arrest and who are on mechanical ventilation in the intensive care unit will be enrolled, and will get either thiamine or placebo. Their oxygen consumption and lactate will be measured at serial time points and compared between groups. The investigators' hypothesis is that thiamine will help restore the body's ability to metabolize oxygen normally (aerobic metabolism), leading to an increase in oxygen consumption and a decrease in lactate.
In-hospital cardiac arrest often leads to shock and organ failure, and low oxygen consumption and high lactate are associated with worse outcome. Thiamine is a B vitamin necessary to maintain the body's ability to use oxygen effectively, and the investigators have found that many patients are thiamine deficient after cardiac arrest. The investigators have also found that thiamine can decrease lactate in thiamine-deficient patients who are critically ill. Patients in this study will be randomized to receive either thiamine or placebo every 12 hours for 2 days after surviving an in-hospital cardiac arrest. The investigators will measure oxygen consumption continuously during that time with a monitor attached to the ventilator tubing, and will also measure lactate and other lab values at several time points.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Thiamine | Experimental | Intervention: Thiamine 500mg IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. |
|
| Placebo | Placebo Comparator | Intervention: Placebo (100mL normal saline) IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thiamine | Drug | Thiamine 500mg IV twice daily for 2 days |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Lactate | The investigators will evaluate the median lactate level over two days, compared between groups | 2 days |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygen Consumption | The investigators will evaluate the mean oxygen consumption over two days, compared between groups | 2 days |
| Pyruvate Dehydrogenase | The investigators will evaluate the median pyruvate dehydrogenase levels over two days, compared between groups |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Katherine M Berg, MD | Beth | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Thiamine | Intervention: Thiamine 500mg IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. Thiamine: Thiamine 500mg IV twice daily for 2 days |
| FG001 | Placebo | Intervention: Placebo (100mL normal saline) IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. placebo: 100mL normal saline IV every 12 hours for 2 days |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Thiamine | Intervention: Thiamine 500mg IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. Thiamine: Thiamine 500mg IV twice daily for 2 days |
| BG001 |
| 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 | The investigators will evaluate the median lactate level over two days, compared between groups | A total of 5 patients in the thiamine group and 4 patients in placebo group missing lactate at 48-hours due to death; these values were imputed using a 20 percent increase prior to calculating the below medians and IQRs. There was one additional patient in the thiamine group whose lactate at 48-hours was not imputed as it was missing due to non-death reasons, leading to n = 17 for thiamine (instead of 18). | Posted | Median | Inter-Quartile Range | mmol/L | 2 days |
|
From enrollment to time of hospital discharge or 90 days, whichever is first.
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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 | Thiamine | Intervention: Thiamine 500mg IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. Thiamine: Thiamine 500mg IV twice daily for 2 days |
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The trial was placed on hold after a data safety and monitoring board (DSMB) review noted possible harm from thiamine in the subgroup of patients with a lactate >5mmol/L at the time of study inclusion, with a similar pattern seen in a companion trial in out-of-hospital cardiac arrest (NCT03450707). While the option of continuing to enroll patients with lactate ≤ 5mmol/L was provided, the trial was terminated formally in August 2022 due to lack of feasibility.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Katherine Berg | BIDMC | 617-754-2281 | kberg@bidmc.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 4, 2022 | Aug 4, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006323 | Heart Arrest |
| D012769 | Shock |
| D000140 | Acidosis, Lactic |
| D001602 | Beriberi |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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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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| placebo | Other | 100mL normal saline IV every 12 hours for 2 days |
|
|
| 2 days |
| Already on thiamine |
|
| Extubated prior to study drug |
|
| Death |
|
| Placebo |
Intervention: Placebo (100mL normal saline) IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. placebo: 100mL normal saline IV every 12 hours for 2 days |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Initial Rhythm | Count of Participants | Participants |
|
| Minutes to Return of Spontaneous Circulation (ROSC) | Median | Inter-Quartile Range | minutes |
|
| OG001 | Placebo | Intervention: Placebo (100mL normal saline) IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. placebo: 100mL normal saline IV every 12 hours for 2 days |
|
|
|
| Secondary | Oxygen Consumption | The investigators will evaluate the mean oxygen consumption over two days, compared between groups | 22 patients had metabolic data at 48 hours, n = 11 in placebo, n = 11 in thiamine | Posted | Mean | Standard Deviation | Area under the Curve VO2 (mL/kg/min) | 2 days |
|
|
|
|
| Secondary | Pyruvate Dehydrogenase | The investigators will evaluate the median pyruvate dehydrogenase levels over two days, compared between groups | Only 12 patients in Thiamine and 13 patients in Placebo alive and with non-missing PDH specific activity values at 48-hours. | Posted | Median | Inter-Quartile Range | mini OD unit/min/mg protein | 2 days |
|
|
|
|
| 12 |
| 18 |
| 0 |
| 18 |
| 0 |
| 18 |
| EG001 | Placebo | Intervention: Placebo (100mL normal saline) IV every 12 hours for 2 days. Oxygen consumption will be monitored with a non-invasive monitor continuously for 2 days and lactate, pyruvate dehydrogenase and other routine lab values will be checked at serial time points. placebo: 100mL normal saline IV every 12 hours for 2 days | 12 | 18 | 0 | 18 | 0 | 18 |
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| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D013832 | Thiamine Deficiency |
| D014804 | Vitamin B Deficiency |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |