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

Summary

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.

Conditions

• Acute Lung Injury, Transfusion Related

Interventions

DRUG

Ascorbic Acid Injectable Product

Intermittent Intravenous Infusion of Ascorbic Acid (Vitamin C) 2.5 gm / 6 hours for 96 hours

DRUG

Placebo

Placebo saline / 6 hours for 96 hours

Sponsors & Collaborators

• Alexandria University

  collaborator OTHER

• Damanhour University

  lead OTHER

Principal Investigators

• Gamal A Omran, PHD · Professor of Biochemistry, Damanhour University.

• Mohamed M Megahed, MD · Professor of Critical Care Medicine, Alexandria University.

• Tamer N Zakhary, MD · Ass. Professor of Critical Care Medicine, Alexandria University.

• Amira B Kassem, PHD · Lecturer of Clinical Pharmacy, Damanhour University.

• Islam E Ahmed, PharmD · Clinical Pharmacy Specialist, Damanhour University.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

64 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-11-30

Primary Completion

2021-07-16

Completion

2021-07-16

Countries

• Egypt