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Completed

NCT Number: NCT02106975

Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury

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).

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Emory University and Grady Memorial Hospital, Atlanta, Georgia, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

ascorbic acid

Drug

Intervention

Other names: Vitamin C

Placebo: 5% Dextrose in water

Drug

Placebo

Primary outcomes

  1. 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.

  2. C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo

    Time frame: up to 168 hours

  3. Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo

    Time frame: Up to 168 hours

Secondary outcomes

  1. 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

  2. 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

  3. 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.

  4. Ascorbate Level at Hour 0, 48, 96, 168

    Time frame: Up to hour 168

  5. Ventilator Free Days to Day 28

    Time frame: Up to Day 28

  6. ICU-free Days at Day 28

    Time frame: Up to Day 28

  7. All Cause Mortality to Day 28

    Time frame: Up to Day 28

  8. Hospital-free Days at Day 60

    Time frame: Up to Day 60

  9. Procalcitonin at Study Hour 0, 48, 96, 168

    Time frame: Up to hour 168

  10. Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168

    Time frame: Up to hour 168

  11. Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168

    Time frame: Up to hour 168

  12. 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

  13. 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

  14. 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

  15. 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

  16. Cardiovascular Function

    Time frame: Up to hour 168

    Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes.

  17. 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

  18. 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

Sponsors and collaborators

Lead sponsor

Virginia Commonwealth University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Acronym: CITRIS-ALI

Important dates

Study start
2014
Primary completion
2017
Study completion
2018
First posted
Apr 8, 2014
Registry last updated
Oct 15, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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