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| ID | Type | Description | Link |
|---|---|---|---|
| 1UM1HL116885-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Hypothesis 1A: Vitamin C infusion will significantly attenuate sepsis-induced systemic organ failure as measured by Sequential Organ Failure Assessment (SOFA) score,
Hypothesis 1B: Vitamin C infusion will attenuate sepsis-induced lung injury as assessed by the oxygenation index and the VE40
Hypothesis 1C: Vitamin C infusion will attenuate biomarkers of inflammation (C-Reactive Protein, Procalcitonin), vascular injury (Thrombomodulin, Angiopoietin-2), alveolar epithelial injury (Receptor for Advanced Glycation Products), while inducing the onset of a fibrinolytic state (Tissue Factor Pathway Inhibitor).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ascorbic Acid | Active Comparator | 200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours |
|
| 5% Dextrose in Water | Placebo Comparator | 50ml every 6 hours for 96 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ascorbic Acid | Drug | Intervention |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Modified Change in Sequential Organ Failure Assessment (mSOFA) Score | mSOFA is a single score based on patient status of five different biological systems: respiratory, cardiovascular, coagulation, renal, and neurological. Scores range from 0 to 20 with higher scores indicated worse status. | 96 hours |
| C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | up to 168 hours | |
| Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | Up to 168 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) at Study Hour 0, 48, 96, 168 if Still Intubated in Ascorbate Infused Patient Compared to Placebo. | Up to hour 168 | |
| VE-40 (Vent RR x TV/Weight) x (PaCO2/40) at Study Hour 0, 48, 96, 168 if Still Intubated, in Ascorbate Infused Patient Compared to Placebo |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alpha B. Fowler, MD | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University and Grady Memorial Hospital | Atlanta | Georgia | 30322 | United States | ||
| University of Kentucky |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31573637 | Derived | Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR 2nd, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko A, Halquist M. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019 Oct 1;322(13):1261-1270. doi: 10.1001/jama.2019.11825. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ascorbic Acid | 200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours Ascorbic Acid: Intervention |
| FG001 | 5% Dextrose in Water | 50ml every 6 hours for 96 hours Placebo: 5% Dextrose in water: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ascorbic Acid | 200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours Ascorbic Acid: Intervention |
| BG001 | 5% Dextrose in Water | 50ml every 6 hours for 96 hours Placebo: 5% Dextrose in water: Placebo |
| 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 | Modified Change in Sequential Organ Failure Assessment (mSOFA) Score | mSOFA is a single score based on patient status of five different biological systems: respiratory, cardiovascular, coagulation, renal, and neurological. Scores range from 0 to 20 with higher scores indicated worse status. | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | score on a scale | 96 hours |
|
All-cause mortality was collected for all days in the ICU, up to 4 days
Due to the high level of adverse events normally associated with patients experiencing Sepsis Induced Acute Lung Injury, other than mortality, only drug related adverse events were tracked.
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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 | Ascorbic Acid | 200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours Ascorbic Acid: Intervention |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alpha A Fowler, III, MD | Virginia Commonwealth University School of Medicine | 804-828-9071 | alpha.fowler@vcuhealth.org |
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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 | Feb 20, 2017 | Jan 2, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D055371 | Acute Lung Injury |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D001205 | Ascorbic Acid |
| D005947 | Glucose |
| D014867 | Water |
| ID | Term |
|---|---|
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Placebo: 5% Dextrose in water | Drug | Placebo |
|
Estimate of Shunt
| Up to hour 168 |
| mSOFA Scores at Hours 0, 48, 96 | mSOFA is a single score based on patient status of five different biological systems: respiratory, cardiovascular, coagulation, renal, and neurological. Scores range from 0 to 20 with higher scores indicated worse status. | Up to hour 96 |
| Ascorbate Level at Hour 0, 48, 96, 168 | Up to hour 168 |
| Ventilator Free Days to Day 28 | Up to Day 28 |
| ICU-free Days at Day 28 | Up to Day 28 |
| All Cause Mortality to Day 28 | Up to Day 28 |
| Hospital-free Days at Day 60 | Up to Day 60 |
| Procalcitonin at Study Hour 0, 48, 96, 168 | Up to hour 168 |
| Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | Up to hour 168 |
| Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | Up to hour 168 |
| Oxygenation Score: Pressure | Oxygenation as measure by the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Scores range from 100 to 300 with lower values indicating more worse outcomes | Up to hour 168 |
| Oxygenation Score: Saturation | Oxygenation as measure by the ratio of arterial oxygen saturation to fraction of inspired oxygen SpO2/FiO2 | Up to hour 168 |
| Coagulation | Coagulation as measured by Platelets per unit of blood. Scores range from less than 20 to more than 150. Lower scores indicate worse outcomes | Up to hour 168 |
| Liver Function | Liver function as measured by Total Bilirubin. Normal levels range from 0.2 - 1.2. Levels greater than 1.2 indicate worse outcomes | Up to hour 168 |
| Cardiovascular Function | Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes. | Up to hour 168 |
| State of Consciousness | State of consciousness as measure by Glasgow Coma Scale which gives a score based on eye, verbal, and motor responses. Scores range from 3 to 15 with lower scores indicating worse outcome | Up to hour 168 |
| Renal Function | Renal function as measured by Creatinine. Scores range from less than 1.2 to greater than 5.0 with higher scores indicating worse outcomes | Up to hour 168 |
| Lexington |
| Kentucky |
| 40506 |
| United States |
| The Cleveland Clinic | Cleveland | Ohio | 44106 | United States |
| Virginia Commonwealth University Health System | Richmond | Virginia | 23298 | United States |
| Froedtert and The Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
50ml every 6 hours for 96 hours
Placebo: 5% Dextrose in water: Placebo
|
|
| Primary | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | µg/ml | up to 168 hours |
|
|
|
| Primary | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | Posted | Mean | Standard Deviation | ng/ml | Up to 168 hours |
|
|
|
| Secondary | Oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) at Study Hour 0, 48, 96, 168 if Still Intubated in Ascorbate Infused Patient Compared to Placebo. | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | Index | Up to hour 168 |
|
|
|
| Secondary | VE-40 (Vent RR x TV/Weight) x (PaCO2/40) at Study Hour 0, 48, 96, 168 if Still Intubated, in Ascorbate Infused Patient Compared to Placebo | Estimate of Shunt | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | mmMercury | Up to hour 168 |
|
|
|
| Secondary | mSOFA Scores at Hours 0, 48, 96 | mSOFA is a single score based on patient status of five different biological systems: respiratory, cardiovascular, coagulation, renal, and neurological. Scores range from 0 to 20 with higher scores indicated worse status. | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Median | Inter-Quartile Range | units on a scale | Up to hour 96 |
|
|
|
| Secondary | Ascorbate Level at Hour 0, 48, 96, 168 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | µM | Up to hour 168 |
|
|
|
| Secondary | Ventilator Free Days to Day 28 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | days | Up to Day 28 |
|
|
|
| Secondary | ICU-free Days at Day 28 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | days | Up to Day 28 |
|
|
|
| Secondary | All Cause Mortality to Day 28 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Number | percentage of participants | Up to Day 28 |
|
|
|
| Secondary | Hospital-free Days at Day 60 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | days | Up to Day 60 |
|
|
|
| Secondary | Procalcitonin at Study Hour 0, 48, 96, 168 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | ng/ml | Up to hour 168 |
|
|
|
| Secondary | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | ng/ml | Up to hour 168 |
|
|
|
| Secondary | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | ng/ml | Up to hour 168 |
|
|
|
| Secondary | Oxygenation Score: Pressure | Oxygenation as measure by the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Scores range from 100 to 300 with lower values indicating more worse outcomes | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | mm Mercury | Up to hour 168 |
|
|
|
| Secondary | Oxygenation Score: Saturation | Oxygenation as measure by the ratio of arterial oxygen saturation to fraction of inspired oxygen SpO2/FiO2 | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | Ratio | Up to hour 168 |
|
|
|
| Secondary | Coagulation | Coagulation as measured by Platelets per unit of blood. Scores range from less than 20 to more than 150. Lower scores indicate worse outcomes | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | Platelets/uL of Blood | Up to hour 168 |
|
|
|
| Secondary | Liver Function | Liver function as measured by Total Bilirubin. Normal levels range from 0.2 - 1.2. Levels greater than 1.2 indicate worse outcomes | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Median | Full Range | Mg/dL | Up to hour 168 |
|
|
|
| Secondary | Cardiovascular Function | Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes. | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Mean | Standard Deviation | mmHg | Up to hour 168 |
|
|
|
| Secondary | State of Consciousness | State of consciousness as measure by Glasgow Coma Scale which gives a score based on eye, verbal, and motor responses. Scores range from 3 to 15 with lower scores indicating worse outcome | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Median | Full Range | units on a scale | Up to hour 168 |
|
|
|
| Secondary | Renal Function | Renal function as measured by Creatinine. Scores range from less than 1.2 to greater than 5.0 with higher scores indicating worse outcomes | 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient | Posted | Median | Full Range | Mg/dL | Up to hour 168 |
|
|
|
| 25 |
| 84 |
| 0 |
| 84 |
| 0 |
| 84 |
| EG001 | 5% Dextrose in Water | 50ml every 6 hours for 96 hours Placebo: 5% Dextrose in water: Placebo | 38 | 83 | 0 | 83 | 0 | 83 |
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| D018746 |
| Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006880 |
| Hydroxy Acids |
| D002241 | Carbohydrates |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|
| 96 hours |
|
| 168 hours |
|