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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Virginia Commonwealth University
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT02106975
First received: March 27, 2014
Last updated: April 17, 2017
Last verified: April 2017
  Purpose

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).


Condition Intervention Phase
Acute Lung Injury
Sepsis
Drug: Ascorbic Acid
Drug: Placebo: 5% Dextrose in water
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Change in SOFA score at 96 hours as compared to baseline when compared to placebo [ Time Frame: 96 hours ]
  • C-Reactive Protein and Thrombomodulin at study hours 0, 48, 96, 168 when compared to placebo [ Time Frame: Up to hour 168 ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]
  • SOFA scores at hours 48, 96, 168 [ Time Frame: Up to hour 168 ]
  • Ascorbate level at hour 0, 48, 96, 168 [ Time Frame: Up to hour 168 ]
  • Ventilator Free Days to day 28 [ Time Frame: Up to Day 28 ]
  • ICU-free days at day 28 [ Time Frame: Up to Day 28 ]
  • All cause mortality to day 28 [ Time Frame: Up to Day 28 ]
  • Hospital-free days at day 60 [ Time Frame: Up to Day 60 ]
  • Procalcitonin at study hour 0, 48, 96, 168 [ Time Frame: Up to hour 168 ]
  • Receptor for Advanced Glycation Endpoints at study hour 0, 48, 96, 168 [ Time Frame: Up to hour 168 ]
  • Tissue factor pathway inhibitor at study hour 0, 48, 96, 168 [ Time Frame: Up to hour 168 ]
  • SOFA Score Component at hours 48,96, 168: PaO2/FiO2 [ Time Frame: Up to hour 168 ]
  • SOFA Score Components at hours 48,96, 168: SpO2/FiO2 [ Time Frame: Up to hour 168 ]
  • SOFA Score Components at hours 48,96, 168: Platelets [ Time Frame: Up to hour 168 ]
  • SOFA Score Components at hours 48,96, 168: Total Bilirubin [ Time Frame: Up to hour 168 ]
  • SOFA Score Components at hours 48,96, 168: Vasopressor status [ Time Frame: Up to hour 168 ]
  • SOFA Score Components at hours 48,96, 168: GCS [ Time Frame: Up to hour 168 ]
  • SOFA Score Components at hours 48,96, 168: Creatinine or Urine Output [ Time Frame: Up to hour 168 ]

Estimated Enrollment: 170
Study Start Date: April 2014
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ascorbic Acid
200mg/kg/day divided over 4 doses. Administered every 6 hours for 96 hours
Drug: Ascorbic Acid
Intervention
Other Name: Vitamin C
Placebo Comparator: 5% Dextrose in Water
50ml every 6 hours for 96 hours
Drug: Placebo: 5% Dextrose in water
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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-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
  • 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:

  • Known allergy to Vitamin C
  • inability to obtain consent;
  • age < 18 years;
  • 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
  • primary care givers unwilling/unable to use ARDSnet 6 ml/kg ventilation protocol;
  • Non English speaking;
  • Ward of the state (inmate, other)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02106975

Contacts
Contact: Christine DeWilde, RN 804-628-5710 dewildect@vcu.edu

Locations
United States, Georgia
Emory University and Grady Memorial Hospital Terminated
Atlanta, Georgia, United States, 30322
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40506
Contact: Peter E. Morris, MD    859-323-5045    peter.morris@uky.edu   
Contact: Evan Cassity    859-218-6683    evan.cassity@uky.edu   
United States, Ohio
The Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44106
Contact: Duncan Hite, MD    216-445-3098    hited@ccf.org   
Contact: Michelle Ferrari, RN    216-445-1939    ferrarm1@ccf.org   
Principal Investigator: Duncan Hite, MD         
United States, Virginia
Virginia Commonwealth University Health System Recruiting
Richmond, Virginia, United States, 23298
Contact: Chris DeWilde, MSN, RN    804-628-5710    christine.dewilde@vcuhealth.org   
Contact: Alpha (Berry) Fowler, MD    804-628-5161    alpha.fowler@vcuhealth.org   
Principal Investigator: Alpha (Berry) Fowler, MD         
Sub-Investigator: Aamer Syed, MD         
United States, Wisconsin
Froedtert and The Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Jonathon Truwit, MD       jonathon.truwit@froedtert.com   
Contact: Jeanette Graf    414-955-6987    jgraf@mcw.edu   
Principal Investigator: Jonathon Truwit, MD         
Sponsors and Collaborators
Virginia Commonwealth University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Alpha B. Fowler, MD Virginia Commonwealth University
  More Information

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02106975     History of Changes
Other Study ID Numbers: HM20000917
1UM1HL116885-01 ( US NIH Grant/Contract Award Number )
Study First Received: March 27, 2014
Last Updated: April 17, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Wounds and Injuries
Sepsis
Toxemia
Lung Injury
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Respiration Disorders
Vitamins
Ascorbic Acid
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on April 28, 2017