Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRIS-ALI)
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).
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Emory University and Grady Memorial Hospital
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-
Kentucky
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Lexington, Kentucky, United States, 40506
- University of Kentucky
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Ohio
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Cleveland, Ohio, United States, 44106
- The Cleveland Clinic
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Virginia
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University Health System
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Froedtert and the Medical College of Wisconsin
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
ACTIVE_COMPARATOR: Ascorbic Acid
200mg/kg/day divided over 4 doses.
Administered every 6 hours for 96 hours
|
Intervention
Other Names:
|
|
PLACEBO_COMPARATOR: 5% Dextrose in Water
50ml every 6 hours for 96 hours
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Placebo
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Modified Change in Sequential Organ Failure Assessment (mSOFA) Score
Time Frame: 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.
|
96 hours
|
|
C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo
Time Frame: up to 168 hours
|
up to 168 hours
|
|
|
Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo
Time Frame: Up to 168 hours
|
Up to 168 hours
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Oxygenation Score: Pressure
Time Frame: 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
|
Up to hour 168
|
|
Coagulation
Time Frame: 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
|
Up to hour 168
|
|
Cardiovascular Function
Time Frame: Up to hour 168
|
Cardiovascular function as measured by Mean arterial pressure.
Scores less than 70 mmHg indicate worse outcomes.
|
Up to hour 168
|
|
State of Consciousness
Time Frame: 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
|
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.
Time Frame: Up to hour 168
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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
Time Frame: Up to hour 168
|
Estimate of Shunt
|
Up to hour 168
|
|
mSOFA Scores at Hours 0, 48, 96
Time Frame: 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.
|
Up to hour 96
|
|
Ascorbate Level at Hour 0, 48, 96, 168
Time Frame: Up to hour 168
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Up to hour 168
|
|
|
Ventilator Free Days to Day 28
Time Frame: Up to Day 28
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Up to Day 28
|
|
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ICU-free Days at Day 28
Time Frame: Up to Day 28
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Up to Day 28
|
|
|
All Cause Mortality to Day 28
Time Frame: Up to Day 28
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Up to Day 28
|
|
|
Hospital-free Days at Day 60
Time Frame: Up to Day 60
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Up to Day 60
|
|
|
Procalcitonin at Study Hour 0, 48, 96, 168
Time Frame: Up to hour 168
|
Up to hour 168
|
|
|
Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168
Time Frame: Up to hour 168
|
Up to hour 168
|
|
|
Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168
Time Frame: Up to hour 168
|
Up to hour 168
|
|
|
Oxygenation Score: Saturation
Time Frame: Up to hour 168
|
Oxygenation as measure by the ratio of arterial oxygen saturation to fraction of inspired oxygen SpO2/FiO2
|
Up to hour 168
|
|
Liver Function
Time Frame: 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
|
Up to hour 168
|
|
Renal Function
Time Frame: 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
|
Up to hour 168
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Principal Investigator: Alpha B. Fowler, MD, Virginia Commonwealth University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (ACTUAL)
Primary Completion
Study Completion (ACTUAL)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
First Posted
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Respiratory Tract Diseases
- Lung Diseases
- Systemic Inflammatory Response Syndrome
- Inflammation
- Thoracic Injuries
- Sepsis
- Toxemia
- Wounds and Injuries
- Acute Lung Injury
- Lung Injury
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Ascorbic Acid
Other Study ID Numbers
Other Study ID Numbers
- HM20000917
- 1UM1HL116885-01 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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