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

July 17, 2023 updated by: Damanhour University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  1. Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
  2. The minimum required sample size is estimated to be 40 patients for each group.
  3. Full written informed consent will be taken from all patients or their next of kin to participate in this study.

  4. All patients will be subjected directly at time of enrollment to the following;

    • Complete history taking and demographic data
    • The potential recipient risk factors for TRALI.
    • The initial cause of ICU admission and the blood products received.
    • Complete physical examination including chest auscultations.
    • Vital signs
    • Routine laboratory investigations
    • Brain natriuretic peptide level
    • Troponin T
    • Hypoxic index
    • Acute Physiology and Chronic Health Evaluation version II (APACHE II) score.
    • Sequential Organ Failure Assessment (SOFA) score.
    • Kidney Disease Improving Global Outcomes (KDIGO) criteria.
    • Child Pugh score.
    • Chest radiography and transthoracic echocardiography.
  5. Samples will be drawn to measure the initial values of ascorbate level, plasma IL-8, IL-10, IL-1β, SOD, MDA and serum CRP.

  6. Eighty patients with confirmed TRALI (n=80) will be enrolled from critical care units (tertiary hospitals). Then, in addition to their supportive and standard care, they will be randomized (computer sheet) into two groups:

    • ASTRALI (AScorbic acid in TRALI) group (n=40) will receive 2.5 gm vitamin C intravenously every 6 hrs for 96 hrs from diagnosis.
    • Control group (n=40) will receive placebo in similar regimen.
  7. All patients will be followed up and treated during the study time. All relevant routine investigations, supportive measures, medications and ventilatory data will be recorded.
  8. All possible adverse events will be monitored, recorded and managed directly. Hyperoxaluria, microscopic calcium-oxalate crystallization or oxalate nephropathy will be monitored, recorded and managed directly.
  9. After 96 hrs, resampling for ascorbate level and the same biomarkers will be done.
  10. Measuring the study secondary outcomes will include vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality.
  11. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Beheira, Egypt, 22511
        • Damanhour University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Description

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 .

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ASTRALI Group
ASTRALI (AScorbic acid in TRALI) group (n=40)
Drug: Ascorbic Acid Injectable Product
Intermittent Intravenous Infusion of Ascorbic Acid (Vitamin C) 2.5 gm / 6 hours for 96 hours
Other Names:
  • Vitamin C
Placebo Comparator: Control Group
Control group (n=40)
Drug: Placebo
Placebo saline / 6 hours for 96 hours
Other Names:
  • Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Interleukin-8 (IL-8)
Time Frame: 96 hrs
Plasma level of IL-8
96 hrs
Interleukin-10 (IL-10)
Time Frame: 96 hrs
Plasma Level of IL-10
96 hrs
C-reactive protein (CRP)
Time Frame: 96 hrs
Serum level of CRP
96 hrs
Superoxide Dismutase (SOD)
Time Frame: 96 hrs
Plasma Level of SOD
96 hrs
Malondialdehyde (MDA)
Time Frame: 96 hrs
Plasma level of MDA
96 hrs

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vasopressor use (days)
Time Frame: up to 28 days
Duration of circulatory support
up to 28 days
Duration of Mechanical Ventilation (days)
Time Frame: up to 28 days
Duration of ventilatory support
up to 28 days
ICU length of stay (days)
Time Frame: Up to 28 days
Length of stay in ICU
Up to 28 days
7-days Mortality
Time Frame: 7 days
All cause mortality
7 days
28-days Mortality
Time Frame: 28 days
All cause mortality
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Damanhour University

Collaborators

Alexandria University

Investigators

  • Study Director: Gamal A Omran, PHD, Professor of Biochemistry, Damanhour University.
  • Study Director: Mohamed M Megahed, MD, Professor of Critical Care Medicine, Alexandria University.
  • Study Chair: Tamer N Zakhary, MD, Ass. Professor of Critical Care Medicine, Alexandria University.
  • Study Chair: Amira B Kassem, PHD, Lecturer of Clinical Pharmacy, Damanhour University.
  • Principal Investigator: Islam E Ahmed, PharmD, Clinical Pharmacy Specialist, Damanhour University.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2019

Primary Completion (Actual)

July 16, 2021

Study Completion (Actual)

July 16, 2021

Study Registration Dates

First Submitted

November 2, 2019

First Submitted That Met QC Criteria

November 5, 2019

First Posted (Actual)

November 6, 2019

Study Record Updates

Last Update Posted (Actual)

July 19, 2023

Last Update Submitted That Met QC Criteria

July 17, 2023

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASTRALI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The summary of all relevant data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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