Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis

Journal of Translational Medicine

Ramesh Natarajan²  Bernard J Fisher²  Medical Respiratory Intensive Care Unit Nursing¹  Seema Gupta⁴  Donald F Brophy⁵  Erika Martin⁵  Terri L Larus⁶  Christine A Farthing⁶  Christine DeWilde²  Don Farthing⁶  Robin Sculthorpe³  Shelley Knowlson¹  Aamer A Syed²  Alpha A Fowler² 

[1] Department of Critical Care Nursing, Virginia Commonwealth University Health System, Richmond, Virginia, USA;Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, PO Box 980050, Richmond, VA 23298-0050, USA;Investigational Drug Services, Department of Pharmacy Services, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA;Health Diagnostic Laboratory, Richmond, Virginia, USA;Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA;Division of Nephrology, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

关键词: Sepsis;    Organ dysfunction scores;    Multiple organ failure;    Clinical trials phase I as topic;    Biological markers;    Ascorbic acid;   

Others  :  821704
DOI  :  10.1186/1479-5876-12-32

 received in 2013-11-12, accepted in 2014-01-02,  发布年份 2014

【 摘 要 】

Background

Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.

Methods

Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.

Results

Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.

Conclusions

Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.

Trial registration

ClinicalTrials.gov identifier NCT01434121.

【 授权许可】

   
2014 Fowler et al.; licensee BioMed Central Ltd.

【 图 表 】

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