Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury
- Registration Number
- NCT02106975
- Lead Sponsor
- Virginia Commonwealth University
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 170
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ascorbic Acid Ascorbic Acid 200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours
- Primary Outcome Measures
Name Time Method C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo up to 168 hours 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.
Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo Up to 168 hours
- Secondary Outcome Measures
Name Time Method 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.
Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168 Up to hour 168 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
Ventilator Free Days to Day 28 Up to Day 28 Procalcitonin 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 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
ICU-free Days at Day 28 Up to Day 28 Hospital-free Days at Day 60 Up to Day 60 Ascorbate Level at Hour 0, 48, 96, 168 Up to hour 168 All Cause Mortality to Day 28 Up to Day 28 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
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.
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
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
Trial Locations
- Locations (5)
Emory University and Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
The Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Virginia Commonwealth University Health System
🇺🇸Richmond, Virginia, United States
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States