Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury

NCT02106975 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: HM200009171UM1HL116885-01
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 5

Brief 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).

Conditions

Acute Lung Injury; Sepsis

Outcome Measures

Primary Outcomes (3)

• 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

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

  up to 168 hours

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

  Up to 168 hours

Secondary Outcomes (18)

• 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

• 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

  Up to hour 168

• mSOFA Scores at Hours 0, 48, 96

  Up to hour 96

• Ascorbate Level at Hour 0, 48, 96, 168

  Up to hour 168

• Ventilator Free Days to Day 28

  Up to Day 28

Study Arms (2)

Ascorbic Acid

ACTIVE COMPARATOR

200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours

Drug: Ascorbic Acid

5% Dextrose in Water

PLACEBO COMPARATOR

50ml every 6 hours for 96 hours

Drug: Placebo: 5% Dextrose in water

Interventions

Ascorbic Acid DRUG

Intervention

Also known as: Vitamin C

Ascorbic Acid

Placebo: 5% Dextrose in water DRUG

Placebo

5% Dextrose in Water

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

Emory University and Grady Memorial Hospital

Atlanta, Georgia, 30322, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

Virginia Commonwealth University Health System

Richmond, Virginia, 23298, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR 2nd, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko A, Halquist M. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019 Oct 1;322(13):1261-1270. doi: 10.1001/jama.2019.11825.

  PMID: 31573637 DERIVED

MeSH Terms

Conditions

Acute Lung Injury; Sepsis

Interventions

Ascorbic Acid; Glucose; Water

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Hexoses; Monosaccharides; Sugars; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Results Point of Contact

• Title: Alpha A Fowler, III, MD
• Organization: Virginia Commonwealth University School of Medicine

alpha.fowler@vcuhealth.org

804-828-9071

Study Officials

• Alpha B. Fowler, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 8, 2014
• Study Start: April 1, 2014
• Primary Completion: November 16, 2017
• Study Completion: January 8, 2018
• Last Updated: October 15, 2019
• Results First Posted: October 15, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)