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Acute Lung Injury, Transfusion RelatedPhase 2ASTRALINCT04153487

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

A Phase 2 study testing Ascorbic Acid Injectable Product in people with Acute Lung Injury, Transfusion Related, run by Damanhour University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Acute Lung Injury, Transfusion Related
What is being tested?
Ascorbic Acid Injectable Product
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteEgypt
Study dates
30 Nov 2019to 16 Jul 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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 .

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • Damanhour University

    Beheira, 22511

Other trials in Egypt

About this study

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.

Read more

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.

Read the 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.
  1. Samples will be drawn to measure the initial values of ascorbate level, plasma IL-8, IL-10, IL-1β, SOD, MDA and serum CRP.
  2. 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.
  1. 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.
  2. 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.
  3. After 96 hrs, resampling for ascorbate level and the same biomarkers will be done.
  4. Measuring the study secondary outcomes will include vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality.
  5. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
Being tested
Ascorbic Acid Injectable Product, Placebo
Keywords
Transfusion Reaction, Transfusion Related Complication, Acute Lung Injury, Critical Care
Medical subject headings
Transfusion-Related Acute Lung Injury, Transfusion Reaction, Acute Lung Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ascorbic Acid Injectable ProductDrug

    Also called Vitamin C

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

  • PlaceboDrug

    Also called Normal saline

    Placebo saline / 6 hours for 96 hours

Study groups in NCT04153487
Study groupRoleWhat they receive
ASTRALI GroupExperimentalASTRALI (AScorbic acid in TRALI) group (n=40)
Receives: Drug: Ascorbic Acid Injectable Product
Control GroupPlacebo comparatorControl group (n=40)
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Interleukin-8 (IL-8)

    Plasma level of IL-8

    Measured: 96 hrs

  2. Interleukin-10 (IL-10)

    Plasma Level of IL-10

    Measured: 96 hrs

  3. C-reactive protein (CRP)

    Serum level of CRP

    Measured: 96 hrs

  4. Superoxide Dismutase (SOD)

    Plasma Level of SOD

    Measured: 96 hrs

  5. Malondialdehyde (MDA)

    Plasma level of MDA

    Measured: 96 hrs

Secondary outcomes (5)
  1. Vasopressor use (days)

    Duration of circulatory support

    Measured: up to 28 days

  2. Duration of Mechanical Ventilation (days)

    Duration of ventilatory support

    Measured: up to 28 days

  3. ICU length of stay (days)

    Length of stay in ICU

    Measured: Up to 28 days

  4. 7-days Mortality

    All cause mortality

    Measured: 7 days

  5. 28-days Mortality

    All cause mortality

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2019
  2. Study start30 Nov 2019
  3. Primary completion16 Jul 2021
  4. Study completion16 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized Controlled Trial
Masking
Single blind
Who is masked
Participant
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04153487
Sponsor's protocol ID
ASTRALI
Acronym
ASTRALI
Status last verified
May 2021
First submitted
2 Nov 2019
Last updated
19 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The summary of all relevant data

Publications

  • Peters AL, Van Stein D, Vlaar AP. Antibody-mediated transfusion-related acute lung injury; from discovery to prevention. Br J Haematol. 2015 Sep;170(5):597-614. doi: 10.1111/bjh.13459. Epub 2015 Apr 28.

    PubMed 25921271
  • Vlaar AP, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet. 2013 Sep 14;382(9896):984-94. doi: 10.1016/S0140-6736(12)62197-7. Epub 2013 May 1.

    PubMed 23642914
  • Roubinian N. TACO and TRALI: biology, risk factors, and prevention strategies. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):585-594. doi: 10.1182/asheducation-2018.1.585. Epub 2018 Dec 14.

    PubMed 30570487
  • Peters AL, van Hezel ME, Juffermans NP, Vlaar AP. Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside. Blood Rev. 2015 Jan;29(1):51-61. doi: 10.1016/j.blre.2014.09.007. Epub 2014 Sep 20.

    PubMed 25277811
  • Andreu G, Boudjedir K, Muller JY, Pouchol E, Ozier Y, Fevre G, Gautreau C, Quaranta JF, Drouet C, Rieux C, Mertes PM, Clavier B, Carlier M, Sandid I. Analysis of Transfusion-Related Acute Lung Injury and Possible Transfusion-Related Acute Lung Injury Reported to the French Hemovigilance Network From 2007 to 2013. Transfus Med Rev. 2018 Jan;32(1):16-27. doi: 10.1016/j.tmrv.2017.07.001. Epub 2017 Jul 15.

    PubMed 28864336
  • Vlaar AP, Binnekade JM, Prins D, van Stein D, Hofstra JJ, Schultz MJ, Juffermans NP. Risk factors and outcome of transfusion-related acute lung injury in the critically ill: a nested case-control study. Crit Care Med. 2010 Mar;38(3):771-8. doi: 10.1097/CCM.0b013e3181cc4d4b.

    PubMed 20035217
  • Vlaar APJ, Toy P, Fung M, Looney MR, Juffermans NP, Bux J, Bolton-Maggs P, Peters AL, Silliman CC, Kor DJ, Kleinman S. An update of the transfusion-related acute lung injury (TRALI) definition. Transfus Clin Biol. 2019 Nov;26(4):354-356. doi: 10.1016/j.tracli.2019.05.007. Epub 2019 Jun 12. No abstract available.

    PubMed 31221537
  • Toy P, Gajic O, Bacchetti P, Looney MR, Gropper MA, Hubmayr R, Lowell CA, Norris PJ, Murphy EL, Weiskopf RB, Wilson G, Koenigsberg M, Lee D, Schuller R, Wu P, Grimes B, Gandhi MJ, Winters JL, Mair D, Hirschler N, Sanchez Rosen R, Matthay MA; TRALI Study Group. Transfusion-related acute lung injury: incidence and risk factors. Blood. 2012 Feb 16;119(7):1757-67. doi: 10.1182/blood-2011-08-370932. Epub 2011 Nov 23.

    PubMed 22117051
  • Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood. 2019 Apr 25;133(17):1840-1853. doi: 10.1182/blood-2018-10-860809. Epub 2019 Feb 26.

    PubMed 30808638
  • Roubinian NH, Looney MR, Kor DJ, Lowell CA, Gajic O, Hubmayr RD, Gropper MA, Koenigsberg M, Wilson GA, Matthay MA, Toy P, Murphy EL; TRALI Study Group. Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions. Transfusion. 2015 Aug;55(8):1838-46. doi: 10.1111/trf.13021. Epub 2015 Feb 23.

    PubMed 25702590
  • Semple JW, McVey MJ, Kim M, Rebetz J, Kuebler WM, Kapur R. Targeting Transfusion-Related Acute Lung Injury: The Journey From Basic Science to Novel Therapies. Crit Care Med. 2018 May;46(5):e452-e458. doi: 10.1097/CCM.0000000000002989.

    PubMed 29384784
  • Ducharme-Crevier L, Lacroix J. Interleukin-1 Receptor Antagonist and Interleukin-1beta: Risk Marker or Risk Factor for Pediatric Acute Respiratory Distress Syndrome? Pediatr Crit Care Med. 2018 Oct;19(10):993-995. doi: 10.1097/PCC.0000000000001713. No abstract available.

    PubMed 30281566
  • Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003 Jun;111(12):1805-12. doi: 10.1172/JCI18921. No abstract available.

    PubMed 12813013
  • Kapur R, Kim M, Shanmugabhavananthan S, Liu J, Li Y, Semple JW. C-reactive protein enhances murine antibody-mediated transfusion-related acute lung injury. Blood. 2015 Dec 17;126(25):2747-51. doi: 10.1182/blood-2015-09-672592. Epub 2015 Oct 9.

    PubMed 26453659
  • Kapur R, Kim M, Rondina MT, Porcelijn L, Semple JW. Elevation of C-reactive protein levels in patients with transfusion-related acute lung injury. Oncotarget. 2016 Nov 22;7(47):78048-78054. doi: 10.18632/oncotarget.12872.

    PubMed 27793007

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ascorbic Acid Injectable Product in people with Acute Lung Injury, Transfusion Related, run by Damanhour University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Interleukin-8 (IL-8) (time frame: 96 hrs). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04153487, which also lists 37 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.

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