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

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

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

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).

Participant Eligibility

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).

  1. Suspected or proven infection: (e.g., thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and central nervous system, see Appendix A).
  2. 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.
  3. The presence of sepsis-induced organ dysfunction: (any of the following thought to be due to infection)
    • Sepsis-induced 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
  4. 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

Exclusion Criteria:

  1. Known allergy to Vitamin C
  2. inability to obtain consent;
  3. age < 18 years;
  4. more than 7 days since starting mechanical ventilation;
  5. more than 48 hrs since meeting ARDS criteria;
  6. patient or surrogate or physician not committed to full support (not excluded if patient would receive all supportive care except for cardiac resuscitation);
  7. pregnancy or breast feeding,
  8. moribund patient not expected to survive 24 hours;
  9. home mechanical ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP used only for sleep-disordered breathing;
  10. home O2, except for with CPAP/BIPAP
  11. BMI > 40
  12. diffuse alveolar hemorrhage (vasculitis);
  13. interstitial lung disease requiring continuous home oxygen therapy;
  14. Active kidney stone
  15. primary care givers unwilling/unable to use ARDSnet 6 ml/kg ventilation protocol;
  16. Non English speaking;
  17. Ward of the state (inmate, other)

Study ID: NCT02106975

Study Sites
Medical College of Wisconsin

Principal Investigator(s)
Jonathon Truwit, MD

Contact
Jeanette Graf
414-955-6987
jgraf@mcw.edu