Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRIS-ALI)
This study is currently recruiting participants.
Verified May 2017 by Virginia Commonwealth University
Sponsor:
Virginia Commonwealth University
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: May 3, 2017
Last verified: May 2017
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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:
Genetic and Rare Diseases Information Center resources:
Acute Respiratory Distress Syndrome
Respiratory Distress Syndrome, Infant
U.S. FDA Resources
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
|
| 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 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 noninvasely 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)
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
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 |
| Responsible Party: | Virginia Commonwealth University |
| ClinicalTrials.gov Identifier: | NCT02106975 History of Changes |
| Other Study ID Numbers: |
HM20000917 1UM1HL116885-01 ( U.S. NIH Grant/Contract ) |
| Study First Received: | March 27, 2014 |
| Last Updated: | May 3, 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | 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 July 06, 2017