Role of Ascorbic Acid Infusion in Critically Ill Patients With Transfusion Related Acute Lung Injury

ASTRALI

TRALI was defined as "acute noncardiogenic pulmonary edema typically occurs ≤ 6 hours following transfusion of plasma-containing blood products, such as packed red blood cells, fresh frozen plasma, platelets, or cryoprecipitate." In critically ill patients, TRALI remains the leading cause of transfusion-related fatalities and is accompanied by a very significant morbidity and mortality. Survival in such patients is as low as 53% compared with 83% in acute lung injury (ALI) controls. The incidence of TRALi is likely underreported. In densely populated developing countries, incidence has not decreased due to lack of male-only strategy for plasma donation. TRALI is associated with systemic inflammation characterized by low anti-inflammatory cytokine as interleukin (IL)-10, increased pro-inflammatory cytokine as IL-8. Regulation of inflammation should include avoidance of overproduction of inflammatory mediators. So, it can be dampened not only by increasing IL-10 but also by decreasing IL-1β release. C-reactive protein (CRP) is an acute phase protein which is up-regulated during infections and inflammation. CRP was recently identified as a novel first hit in TRALI. Till now, there is no established treatment for TRALI beyond supportive care and monitoring. Recently, potential therapies have been reviewed, and it was concluded that the most promising therapeutic strategies are IL-10 therapy, downregulation of CRP levels, targeting reactive oxygen species (ROS) or blocking IL-8 receptors. So, antioxidants (such as high dose vitamins), were recommended for future studies as potentially effective treatment. Vitamin C hypovitaminosis is observed in 70% of critically ill despite receiving recommended daily doses. The aim of this study is to investigate the role of intravenous vitamin C (ascorbic acid) as a targeted therapy for transfusion related acute lung injury (TRALI) in critically ill patients in terms of IL-8, IL-10, CRP, SOD, malondialdehyde (MDA), vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality.

2019-11-30

2021-07-16

2021-07-16

Completed

Early phase I

40

Inclusion Criteria: * Adult (18 - 64 years) critically ill patients diagnosed with transfusion related acute lung injury (TRALI), at the time of enrollment or maximum 6 hours before, according to the National Heart, Lung and Blood Institute (NHLBI) Working Group definitions and or the Canadian Consensus Conference criteria (29, 30) as the following criteria; * No evidence of ALI prior to transfusion. * Onset of ALI ≤ 6 hours following cessation of transfusion. * Hypoxemia, defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mmHg or oxygen saturation ≤ 90% on room air. * Radiographic evidence of bilateral infiltrates. * No evidence of left atrial hypertension. Exclusion Criteria: * Pregnancy or breastfeeding. * Hypernatremia or known hypersensitivity to the study drug. * Parenteral nutrition (total/partial) containing vitamin C. * Active renal stone or history of urolithiasis. * Acute Kidney Injury. * Glucose 6 phosphate dehydrogenase deficiency, iron and copper storage diseases. * Immunocompromised patients (cancer or patients on immunosuppressive drugs). * Moribund patient not expected to survive 24 hours . * Home mechanical ventilation (via tracheotomy or noninvasive) except for Continuous Positive Airway Pressure/ Bilevel Positive Airway Pressure (CPAP/BIPAP) used only for sleep-disordered breathing .

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized Controlled Trial', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': 'single (participant)', 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 40, 'type': 'ACTUAL'}}

2023-07-19