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

Primary Purpose

Acute Lung Injury, Transfusion Related

Status

Completed

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Ascorbic Acid Injectable Product

Placebo

About this trial

This is an interventional treatment trial for Acute Lung Injury, Transfusion Related focused on measuring Transfusion Reaction, Transfusion Related Complication, Acute Lung Injury, Critical Care

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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 .

Sites / Locations

Damanhour University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ASTRALI Group

Control Group

Arm Description

ASTRALI (AScorbic acid in TRALI) group (n=40)

Control group (n=40)

Outcomes

Primary Outcome Measures

Interleukin-8 (IL-8)

Plasma level of IL-8

Interleukin-10 (IL-10)

Plasma Level of IL-10

C-reactive protein (CRP)

Serum level of CRP

Superoxide Dismutase (SOD)

Plasma Level of SOD

Malondialdehyde (MDA)

Plasma level of MDA

Secondary Outcome Measures

Vasopressor use (days)

Duration of circulatory support

Duration of Mechanical Ventilation (days)

Duration of ventilatory support

ICU length of stay (days)

Length of stay in ICU

7-days Mortality

All cause mortality

28-days Mortality

All cause mortality

Full Information

NCT ID

NCT04153487

First Posted

November 2, 2019

Last Updated

July 17, 2023

Sponsor

Damanhour University

Collaborators

Alexandria University

1. Study Identification

Unique Protocol Identification Number

NCT04153487

Brief Title

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

Acronym

ASTRALI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

November 30, 2019 (Actual)

Primary Completion Date

July 16, 2021 (Actual)

Study Completion Date

July 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Damanhour University

Collaborators

Alexandria University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed Description

Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University. The minimum required sample size is estimated to be 40 patients for each group. Full written informed consent will be taken from all patients or their next of kin to participate in this study. 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. Samples will be drawn to measure the initial values of ascorbate level, plasma IL-8, IL-10, IL-1β, SOD, MDA and serum CRP. 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. 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. 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. After 96 hrs, resampling for ascorbate level and the same biomarkers will be done. Measuring the study secondary outcomes will include vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lung Injury, Transfusion Related

Keywords

Transfusion Reaction, Transfusion Related Complication, Acute Lung Injury, Critical Care

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Randomized Controlled Trial

Masking

Participant

Masking Description

single (participant)

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ASTRALI Group

Arm Type

Experimental

Arm Description

ASTRALI (AScorbic acid in TRALI) group (n=40)

Arm Title

Control Group

Arm Type

Placebo Comparator

Arm Description

Control group (n=40)

Intervention Type

Drug

Intervention Name(s)

Ascorbic Acid Injectable Product

Other Intervention Name(s)

Vitamin C

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Normal saline

Intervention Description

Placebo saline / 6 hours for 96 hours

Primary Outcome Measure Information:

Title

Interleukin-8 (IL-8)

Description

Plasma level of IL-8

Time Frame

96 hrs

Title

Interleukin-10 (IL-10)

Description

Plasma Level of IL-10

Time Frame

96 hrs

Title

C-reactive protein (CRP)

Description

Serum level of CRP

Time Frame

96 hrs

Title

Superoxide Dismutase (SOD)

Description

Plasma Level of SOD

Time Frame

96 hrs

Title

Malondialdehyde (MDA)

Description

Plasma level of MDA

Time Frame

96 hrs

Secondary Outcome Measure Information:

Title

Vasopressor use (days)

Description

Duration of circulatory support

Time Frame

up to 28 days

Title

Duration of Mechanical Ventilation (days)

Description

Duration of ventilatory support

Time Frame

up to 28 days

Title

ICU length of stay (days)

Description

Length of stay in ICU

Time Frame

Up to 28 days

Title

7-days Mortality

Description

All cause mortality

Time Frame

7 days

Title

28-days Mortality

Description

All cause mortality

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 .

Overall Study Officials: