Acute Lung Injury, Sepsis
Conditions
Brief summary
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).
Interventions
DRUGAscorbic Acid
Intervention
DRUGPlacebo: 5% Dextrose in water
Placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have suspected or proven infection, and meet 2 out of 4 of the criteria for Systemic Inflammatory Response (SIRS) due to infection, and be accompanied by at least 1 criterion for sepsis-induced organ dysfunction, and meet all 5 criteria for Acute Respiratory Distress Syndrome (ARDS). * Suspected or proven infection: (e.g., thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and central nervous system, see Appendix A). * The presence of a systemic inflammatory response: Defined as: fever: \>38ºC (any route) or hypothermia: \<36ºC (core temp only), tachycardia: heart rate \> 90 beats/min or receiving medications that slow heart rate or paced rhythm, leukocytosis: \>12,000 WBC/µL or leukopenia: \<4,000 WBC/µL or \>10% band forms. Respiratory rate \> 20 breaths per minute or PaCO2 \< 32 or invasive mechanical ventilation. * The presence of sepsis associated organ dysfunction: (any of the following thought to be due to infection) * Sepsis associated hypotension (systolic blood pressure (SBP) \< 90 mm Hg or an SBP decrease \> 40 mm Hg unexplained by other causes or use of vasopressors for blood pressure support (epinephrine, norepinephrine, dopamine =/\> 5mcg, phenylephrine, vasopressin) * Arterial hypoxemia (PaO2/FiO2 \< 300) or supplemental O2 \> 6LPM. * Lactate \> upper limits of normal laboratory results * Urine output \< 0.5 ml/kg/hour for \> two hours despite adequate fluid resuscitation * Platelet count \< 100,000 per mcL * Coagulopathy (INR \> 1.5) * Bilirubin \> 2 mg/dL * Glasgow Coma Scale \< 11 or a positive CAM ICU score * ARDS characterized by all the following criteria * Lung injury of acute onset, within 1 week of an apparent clinical insult and with progression of respiratory symptoms * Bilateral opacities on chest imaging not explained by other pulmonary pathology (e.g. pleural effusions, lung collapse, or nodules) * Respiratory failure not explained by heart failure or volume overload * Decreased arterial PaO2/FiO2 ratio ≤ 300 mm Hg * Minimum PEEP of 5 cmH2O (may be delivered noninvasively with CPAP to diagnose mild ARDS
Exclusion criteria
* Known allergy to Vitamin C * inability to obtain consent; * age \< 18 years; * No indwelling venous or arterial catheter in patients requiring insulin in a manner that requires glucose being checked more than twice daily (e.g. continuous infusion, sliding scale); * presence of diabetic ketoacidosis; * more than 48 hrs since meeting ARDS criteria; * patient or surrogate or physician not committed to full support (not excluded if patient would receive all supportive care except for cardiac resuscitation); * pregnancy or breast feeding, * moribund patient not expected to survive 24 hours; * home mechanical ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP used only for sleep-disordered breathing; * home O2 \> 2LPM, except for with CPAP/BIPAP * diffuse alveolar hemorrhage (vasculitis); * interstitial lung disease requiring continuous home oxygen therapy; * Active kidney stone * Non English speaking; * Ward of the state (inmate, other)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Change in Sequential Organ Failure Assessment (mSOFA) Score | 96 hours | 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. |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mSOFA Scores at Hours 0, 48, 96 | Up to hour 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. |
| 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 | — |
| State of Consciousness | Up to hour 168 | 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 |
| Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | Up to hour 168 | — |
| Oxygenation Score: Pressure | Up to hour 168 | 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 |
| Oxygenation Score: Saturation | Up to hour 168 | Oxygenation as measure by the ratio of arterial oxygen saturation to fraction of inspired oxygen SpO2/FiO2 |
| Coagulation | Up to hour 168 | Coagulation as measured by Platelets per unit of blood. Scores range from less than 20 to more than 150. Lower scores indicate worse outcomes |
| Liver Function | Up to hour 168 | Liver function as measured by Total Bilirubin. Normal levels range from 0.2 - 1.2. Levels greater than 1.2 indicate worse outcomes |
| Cardiovascular Function | Up to hour 168 | Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes. |
| Renal Function | Up to hour 168 | Renal function as measured by Creatinine. Scores range from less than 1.2 to greater than 5.0 with higher scores indicating worse outcomes |
| Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | Up to hour 168 | — |
| 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 | Up to hour 168 | Estimate of Shunt |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ascorbic Acid 200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours
Ascorbic Acid: Intervention | 84 |
| 5% Dextrose in Water 50ml every 6 hours for 96 hours
Placebo: 5% Dextrose in water: Placebo | 83 |
| Total | 167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 25 | 39 |
Baseline characteristics
| Characteristic | Ascorbic Acid | Total | 5% Dextrose in Water |
|---|---|---|---|
| Age, Continuous | 54 years | 56 years | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 163 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 32 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 68 Participants | 128 Participants | 60 Participants |
| Region of Enrollment United States | 84 participants | 167 participants | 83 participants |
| Sex: Female, Male Female | 39 Participants | 77 Participants | 38 Participants |
| Sex: Female, Male Male | 45 Participants | 90 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 25 / 84 | 38 / 83 |
| other Total, other adverse events | 0 / 84 | 0 / 83 |
| serious Total, serious adverse events | 0 / 84 | 0 / 83 |
Outcome results
Primary
C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo
Time frame: up to 168 hours
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 0 hours | 109 µg/ml | Standard Deviation 76 |
| Ascorbic Acid | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 48 hours | 80 µg/ml | Standard Deviation 66 |
| Ascorbic Acid | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 96 hours | 56 µg/ml | Standard Deviation 51 |
| Ascorbic Acid | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 168 hours | 54 µg/ml | Standard Deviation 48 |
| 5% Dextrose in Water | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 168 hours | 46 µg/ml | Standard Deviation 33 |
| 5% Dextrose in Water | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 0 hours | 119 µg/ml | Standard Deviation 67 |
| 5% Dextrose in Water | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 96 hours | 59 µg/ml | Standard Deviation 52 |
| 5% Dextrose in Water | C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 48 hours | 84 µg/ml | Standard Deviation 52 |
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.
Time frame: 96 hours
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ascorbic Acid | Modified Change in Sequential Organ Failure Assessment (mSOFA) Score | -2.96 score on a scale | Standard Deviation 4.2 |
| 5% Dextrose in Water | Modified Change in Sequential Organ Failure Assessment (mSOFA) Score | -3.20 score on a scale | Standard Deviation 3.3 |
Primary
Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo
Time frame: Up to 168 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 0 hours | 14 ng/ml | Standard Deviation 11 |
| Ascorbic Acid | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 48 hours | 15 ng/ml | Standard Deviation 11 |
| Ascorbic Acid | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 96 hours | 15 ng/ml | Standard Deviation 10 |
| Ascorbic Acid | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 168 hours | 14 ng/ml | Standard Deviation 9 |
| 5% Dextrose in Water | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 168 hours | 14 ng/ml | Standard Deviation 9 |
| 5% Dextrose in Water | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 0 hours | 14 ng/ml | Standard Deviation 8 |
| 5% Dextrose in Water | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 96 hours | 15 ng/ml | Standard Deviation 10 |
| 5% Dextrose in Water | Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo | 48 hours | 15 ng/ml | Standard Deviation 10 |
Secondary
All Cause Mortality to Day 28
Time frame: Up to Day 28
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ascorbic Acid | All Cause Mortality to Day 28 | 30 percentage of participants |
| 5% Dextrose in Water | All Cause Mortality to Day 28 | 46 percentage of participants |
Secondary
Ascorbate Level at Hour 0, 48, 96, 168
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Ascorbate Level at Hour 0, 48, 96, 168 | 0 hour | 25 µM | Standard Deviation 18 |
| Ascorbic Acid | Ascorbate Level at Hour 0, 48, 96, 168 | 48 hours | 301 µM | Standard Deviation 355 |
| Ascorbic Acid | Ascorbate Level at Hour 0, 48, 96, 168 | 96 hours | 397 µM | Standard Deviation 580 |
| Ascorbic Acid | Ascorbate Level at Hour 0, 48, 96, 168 | 168 hours | 90 µM | Standard Deviation 145 |
| 5% Dextrose in Water | Ascorbate Level at Hour 0, 48, 96, 168 | 168 hours | 28 µM | Standard Deviation 19 |
| 5% Dextrose in Water | Ascorbate Level at Hour 0, 48, 96, 168 | 0 hour | 26 µM | Standard Deviation 19 |
| 5% Dextrose in Water | Ascorbate Level at Hour 0, 48, 96, 168 | 96 hours | 26 µM | Standard Deviation 18 |
| 5% Dextrose in Water | Ascorbate Level at Hour 0, 48, 96, 168 | 48 hours | 24 µM | Standard Deviation 16 |
Secondary
Cardiovascular Function
Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes.
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Cardiovascular Function | 0 hour | 73 mmHg | Standard Deviation 13 |
| Ascorbic Acid | Cardiovascular Function | 96 hours | 84 mmHg | Standard Deviation 16 |
| Ascorbic Acid | Cardiovascular Function | 48 hours | 78 mmHg | Standard Deviation 15 |
| Ascorbic Acid | Cardiovascular Function | 168 hours | 81 mmHg | Standard Deviation 14 |
| 5% Dextrose in Water | Cardiovascular Function | 48 hours | 79 mmHg | Standard Deviation 14 |
| 5% Dextrose in Water | Cardiovascular Function | 0 hour | 73 mmHg | Standard Deviation 10 |
| 5% Dextrose in Water | Cardiovascular Function | 168 hours | 83 mmHg | Standard Deviation 17 |
| 5% Dextrose in Water | Cardiovascular Function | 96 hours | 84 mmHg | Standard Deviation 16 |
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
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Coagulation | 0 hour | 173 Platelets/uL of Blood | Standard Deviation 123 |
| Ascorbic Acid | Coagulation | 48 hours | 171 Platelets/uL of Blood | Standard Deviation 133 |
| Ascorbic Acid | Coagulation | 96 hours | 182 Platelets/uL of Blood | Standard Deviation 141 |
| Ascorbic Acid | Coagulation | 168 hours | 226 Platelets/uL of Blood | Standard Deviation 180 |
| 5% Dextrose in Water | Coagulation | 168 hours | 228 Platelets/uL of Blood | Standard Deviation 127 |
| 5% Dextrose in Water | Coagulation | 0 hour | 175 Platelets/uL of Blood | Standard Deviation 142 |
| 5% Dextrose in Water | Coagulation | 96 hours | 165 Platelets/uL of Blood | Standard Deviation 119 |
| 5% Dextrose in Water | Coagulation | 48 hours | 147 Platelets/uL of Blood | Standard Deviation 115 |
Secondary
Hospital-free Days at Day 60
Time frame: Up to Day 60
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ascorbic Acid | Hospital-free Days at Day 60 | 23 days | Standard Deviation 22 |
| 5% Dextrose in Water | Hospital-free Days at Day 60 | 15 days | Standard Deviation 21 |
Secondary
ICU-free Days at Day 28
Time frame: Up to Day 28
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ascorbic Acid | ICU-free Days at Day 28 | 11 days | Standard Deviation 10 |
| 5% Dextrose in Water | ICU-free Days at Day 28 | 8 days | Standard Deviation 9 |
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
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ascorbic Acid | Liver Function | 0 hour | 1 Mg/dL |
| Ascorbic Acid | Liver Function | 48 hours | 1 Mg/dL |
| Ascorbic Acid | Liver Function | 96 hours | 1 Mg/dL |
| Ascorbic Acid | Liver Function | 168 hours | 1 Mg/dL |
| 5% Dextrose in Water | Liver Function | 168 hours | 1 Mg/dL |
| 5% Dextrose in Water | Liver Function | 0 hour | 1 Mg/dL |
| 5% Dextrose in Water | Liver Function | 96 hours | 1 Mg/dL |
| 5% Dextrose in Water | Liver Function | 48 hours | 1 Mg/dL |
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.
Time frame: Up to hour 96
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ascorbic Acid | mSOFA Scores at Hours 0, 48, 96 | 0 hours | 10 units on a scale |
| Ascorbic Acid | mSOFA Scores at Hours 0, 48, 96 | 48 hours | 9 units on a scale |
| Ascorbic Acid | mSOFA Scores at Hours 0, 48, 96 | 96 hours | 6 units on a scale |
| 5% Dextrose in Water | mSOFA Scores at Hours 0, 48, 96 | 0 hours | 10 units on a scale |
| 5% Dextrose in Water | mSOFA Scores at Hours 0, 48, 96 | 48 hours | 8 units on a scale |
| 5% Dextrose in Water | mSOFA Scores at Hours 0, 48, 96 | 96 hours | 6 units on a scale |
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.
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | 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. | 0 hour | 11 Index | Standard Deviation 10 |
| Ascorbic Acid | 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. | 48 hours | 7 Index | Standard Deviation 5 |
| Ascorbic Acid | 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. | 96 hours | 9 Index | Standard Deviation 6 |
| Ascorbic Acid | 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. | 168 hours | 8 Index | Standard Deviation 8 |
| 5% Dextrose in Water | 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. | 168 hours | 8 Index | Standard Deviation 6 |
| 5% Dextrose in Water | 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. | 0 hour | 10 Index | Standard Deviation 6 |
| 5% Dextrose in Water | 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. | 96 hours | 7 Index | Standard Deviation 8 |
| 5% Dextrose in Water | 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. | 48 hours | 7 Index | Standard Deviation 5 |
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
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Oxygenation Score: Pressure | 0 hour | 189 mm Mercury | Standard Deviation 96 |
| Ascorbic Acid | Oxygenation Score: Pressure | 48 hours | 233 mm Mercury | Standard Deviation 115 |
| Ascorbic Acid | Oxygenation Score: Pressure | 96 hours | 226 mm Mercury | Standard Deviation 109 |
| Ascorbic Acid | Oxygenation Score: Pressure | 168 hours | 233 mm Mercury | Standard Deviation 134 |
| 5% Dextrose in Water | Oxygenation Score: Pressure | 168 hours | 254 mm Mercury | Standard Deviation 145 |
| 5% Dextrose in Water | Oxygenation Score: Pressure | 0 hour | 214 mm Mercury | Standard Deviation 183 |
| 5% Dextrose in Water | Oxygenation Score: Pressure | 96 hours | 244 mm Mercury | Standard Deviation 122 |
| 5% Dextrose in Water | Oxygenation Score: Pressure | 48 hours | 246 mm Mercury | Standard Deviation 105 |
Secondary
Oxygenation Score: Saturation
Oxygenation as measure by the ratio of arterial oxygen saturation to fraction of inspired oxygen SpO2/FiO2
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Oxygenation Score: Saturation | 0 hour | 168 Ratio | Standard Deviation 51 |
| Ascorbic Acid | Oxygenation Score: Saturation | 48 hours | 231 Ratio | Standard Deviation 81 |
| Ascorbic Acid | Oxygenation Score: Saturation | 96 hours | 250 Ratio | Standard Deviation 101 |
| Ascorbic Acid | Oxygenation Score: Saturation | 168 hours | 268 Ratio | Standard Deviation 107 |
| 5% Dextrose in Water | Oxygenation Score: Saturation | 168 hours | 299 Ratio | Standard Deviation 115 |
| 5% Dextrose in Water | Oxygenation Score: Saturation | 0 hour | 177 Ratio | Standard Deviation 106 |
| 5% Dextrose in Water | Oxygenation Score: Saturation | 96 hours | 244 Ratio | Standard Deviation 88 |
| 5% Dextrose in Water | Oxygenation Score: Saturation | 48 hours | 220 Ratio | Standard Deviation 75 |
Secondary
Procalcitonin at Study Hour 0, 48, 96, 168
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Procalcitonin at Study Hour 0, 48, 96, 168 | 0 hour | 12 ng/ml | Standard Deviation 23 |
| Ascorbic Acid | Procalcitonin at Study Hour 0, 48, 96, 168 | 48 hours | 7 ng/ml | Standard Deviation 18 |
| Ascorbic Acid | Procalcitonin at Study Hour 0, 48, 96, 168 | 96 hours | 3 ng/ml | Standard Deviation 6 |
| Ascorbic Acid | Procalcitonin at Study Hour 0, 48, 96, 168 | 168 hours | 2 ng/ml | Standard Deviation 3 |
| 5% Dextrose in Water | Procalcitonin at Study Hour 0, 48, 96, 168 | 168 hours | 3 ng/ml | Standard Deviation 11 |
| 5% Dextrose in Water | Procalcitonin at Study Hour 0, 48, 96, 168 | 0 hour | 27 ng/ml | Standard Deviation 69 |
| 5% Dextrose in Water | Procalcitonin at Study Hour 0, 48, 96, 168 | 96 hours | 4 ng/ml | Standard Deviation 9 |
| 5% Dextrose in Water | Procalcitonin at Study Hour 0, 48, 96, 168 | 48 hours | 9 ng/ml | Standard Deviation 20 |
Secondary
Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 0 hour | 6 ng/ml | Standard Deviation 5 |
| Ascorbic Acid | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 48 hours | 4 ng/ml | Standard Deviation 4 |
| Ascorbic Acid | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 96 hours | 4 ng/ml | Standard Deviation 3 |
| Ascorbic Acid | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 168 hours | 3 ng/ml | Standard Deviation 2 |
| 5% Dextrose in Water | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 168 hours | 2 ng/ml | Standard Deviation 2 |
| 5% Dextrose in Water | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 0 hour | 7 ng/ml | Standard Deviation 5 |
| 5% Dextrose in Water | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 96 hours | 3 ng/ml | Standard Deviation 2 |
| 5% Dextrose in Water | Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 | 48 hours | 4 ng/ml | Standard Deviation 3 |
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
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ascorbic Acid | Renal Function | 0 hour | 1 Mg/dL |
| Ascorbic Acid | Renal Function | 48 hours | 2 Mg/dL |
| Ascorbic Acid | Renal Function | 96 hours | 1 Mg/dL |
| Ascorbic Acid | Renal Function | 168 hours | 1 Mg/dL |
| 5% Dextrose in Water | Renal Function | 168 hours | 1 Mg/dL |
| 5% Dextrose in Water | Renal Function | 0 hour | 2 Mg/dL |
| 5% Dextrose in Water | Renal Function | 96 hours | 1 Mg/dL |
| 5% Dextrose in Water | Renal Function | 48 hours | 1 Mg/dL |
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
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ascorbic Acid | State of Consciousness | 0 hour | 8 units on a scale |
| Ascorbic Acid | State of Consciousness | 48 hours | 9 units on a scale |
| Ascorbic Acid | State of Consciousness | 96 hours | 10 units on a scale |
| Ascorbic Acid | State of Consciousness | 168 hours | 10 units on a scale |
| 5% Dextrose in Water | State of Consciousness | 168 hours | 12 units on a scale |
| 5% Dextrose in Water | State of Consciousness | 0 hour | 7 units on a scale |
| 5% Dextrose in Water | State of Consciousness | 96 hours | 10 units on a scale |
| 5% Dextrose in Water | State of Consciousness | 48 hours | 9 units on a scale |
Secondary
Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 0 hour | 46 ng/ml | Standard Deviation 35 |
| Ascorbic Acid | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 48 hours | 42 ng/ml | Standard Deviation 31 |
| Ascorbic Acid | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 96 hours | 42 ng/ml | Standard Deviation 27 |
| Ascorbic Acid | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 168 hours | 44 ng/ml | Standard Deviation 34 |
| 5% Dextrose in Water | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 168 hours | 42 ng/ml | Standard Deviation 31 |
| 5% Dextrose in Water | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 0 hour | 43 ng/ml | Standard Deviation 28 |
| 5% Dextrose in Water | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 96 hours | 44 ng/ml | Standard Deviation 28 |
| 5% Dextrose in Water | Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168 | 48 hours | 42 ng/ml | Standard Deviation 33 |
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
Time frame: Up to hour 168
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ascorbic Acid | 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 | 0 hour | 127 mmMercury | Standard Deviation 58 |
| Ascorbic Acid | 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 | 48 hours | 127 mmMercury | Standard Deviation 63 |
| Ascorbic Acid | 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 | 96 hours | 127 mmMercury | Standard Deviation 47 |
| Ascorbic Acid | 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 | 168 hours | 115 mmMercury | Standard Deviation 54 |
| 5% Dextrose in Water | 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 | 168 hours | 131 mmMercury | Standard Deviation 77 |
| 5% Dextrose in Water | 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 | 0 hour | 121 mmMercury | Standard Deviation 60 |
| 5% Dextrose in Water | 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 | 96 hours | 114 mmMercury | Standard Deviation 46 |
| 5% Dextrose in Water | 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 | 48 hours | 123 mmMercury | Standard Deviation 51 |
Secondary
Ventilator Free Days to Day 28
Time frame: Up to Day 28
Population: 3 participants were omitted from the analysis because the etiology of the patients SEPSIS was not representative of the typical SEPSIS patient
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ascorbic Acid | Ventilator Free Days to Day 28 | 13 days | Standard Deviation 11 |
| 5% Dextrose in Water | Ventilator Free Days to Day 28 | 11 days | Standard Deviation 11 |