Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury

Sepsis Clinical Trial

— CITRIS-ALI  

Official title:

Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02106975
• Other study ID #: HM20000917
• Secondary ID: 1UM1HL116885-01
• Status: Completed
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: January 8, 2018

Study information

• Verified date: October 2019
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: January 8, 2018
• Est. primary completion date: November 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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).

• 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)

Related Conditions & MeSH terms

• Acute Lung Injury
• Lung Injury
• Respiratory Distress Syndrome, Adult
• Sepsis
• Toxemia
• Wounds and Injuries

Intervention

Drug:
• Ascorbic Acid
Intervention
• Placebo: 5% Dextrose in water
Placebo

Locations

Country	Name	City	State
United States	Emory University and Grady Memorial Hospital	Atlanta	Georgia
United States	The Cleveland Clinic	Cleveland	Ohio
United States	University of Kentucky	Lexington	Kentucky
United States	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Virginia Commonwealth University Health System	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Change in Sequential Organ Failure Assessment (mSOFA) Score	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
Primary	C-Reactive Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo		up to 168 hours
Primary	Thrombomodulin Protein at Study Hours 0, 48, 96, 168 When Compared to Placebo		Up to 168 hours
Secondary	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
Secondary	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	Estimate of Shunt	Up to hour 168
Secondary	mSOFA Scores at Hours 0, 48, 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
Secondary	Ascorbate Level at Hour 0, 48, 96, 168		Up to hour 168
Secondary	Ventilator Free Days to Day 28		Up to Day 28
Secondary	ICU-free Days at Day 28		Up to Day 28
Secondary	All Cause Mortality to Day 28		Up to Day 28
Secondary	Hospital-free Days at Day 60		Up to Day 60
Secondary	Procalcitonin at Study Hour 0, 48, 96, 168		Up to hour 168
Secondary	Receptor for Advanced Glycation Endpoints at Study Hour 0, 48, 96, 168		Up to hour 168
Secondary	Tissue Factor Pathway Inhibitor at Study Hour 0, 48, 96, 168		Up to hour 168
Secondary	Oxygenation Score: Pressure	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
Secondary	Oxygenation Score: Saturation	Oxygenation as measure by the ratio of arterial oxygen saturation to fraction of inspired oxygen SpO2/FiO2	Up to hour 168
Secondary	Coagulation	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
Secondary	Liver Function	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
Secondary	Cardiovascular Function	Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes.	Up to hour 168
Secondary	State of Consciousness	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
Secondary	Renal Function	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