Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRIS-ALI)

Virginia Commonwealth University (VCU)

Status and phase

Completed

Phase 2

Conditions

Acute Lung Injury

Sepsis

Treatments

Drug: Ascorbic Acid

Drug: Placebo: 5% Dextrose in water

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02106975

HM20000917

1UM1HL116885-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Enrollment

170 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)