Lactoferrin Use in ICU Patients

NCT05936528 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: MD.23.09.80035039/9/23
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Lactoferrin has several uses due to its effects. It has anti-inflammatory, antioxidant, immunomodulatory, antibacterial, antifungal, and antiviral effects. Its safety is proven by food and drug administration. Aims: The objective is to study the effect of lactoferrin on improving clinical outcomes in ICU patients, and also to evaluate its safety. Patients and populations: A sample of 660 patients (330 patients in both groups A, and B) who will be admitted to ICU departments in Mansoura university hospital will be used to represent the population in ICU. Methods: A sample of 660 participants was randomized 1:1 into two groups (group A (330 patients), and group B (330 patients)). This study is a single blind, randomized controlled clinical trial. Randomization was performed by independent clinical pharmacists working in hospital ICU departments.

Conditions

Critical Illness

Keywords

Clinical outcomes; ICU patients; Lactoferrin; Antioxidant therapy; Anti-inflammatory therapy; Antimicrobial therapy

Outcome Measures

Primary Outcomes (2)

• 28-days mortality rate

  Dead or alive

  28 days

• Number of Participants With any allergic or hypersensitivity reactions

  incidence of any allergic or hypersensitivity reactions

  up to 60 days

Secondary Outcomes (57)

• Day of death

  up to 60 days

• Incidence of need for Invasive Mechanical Ventilation

  up to 60 days

• Oxygen Support Duration

  up to 60 days

• Duration of ICU stay

  up to 60 days

• White blood cells (WBCs) counts on day 3

  day 3

Other Outcomes (12)

• Glasgow Coma Score (GCS) on day 3

  day 3

• Glasgow Coma Score (GCS) on day 7

  day 7

• Glasgow Coma Score (GCS) on day 14

  day 14

Study Arms (2)

Lactoferrin

EXPERIMENTAL

Lactoferrin 100 mg sachets with a dose of 200 mg (2 sachets) orally twice daily (400 mg per day) In addition to standard of care

Drug: Lactoferrin

Standard

ACTIVE COMPARATOR

Subgroup B1 will receive standard antioxidant drug (Acetyl cysteine 600 mg / 12 hr) orally to be compared with lactoferrin A1 subgroup. * Subgroup B2 will receive standard anti-inflammatory, and immunomodulatory drug (dexamethasone I.V 8 mg / day) to be compared with lactoferrin A2 subgroup. * Subgroup B3 will receive standard antibacterial drugs to be compared with lactoferrin A3 subgroup.

Drug: Antioxidant therapies; Drug: Dexamethasone; Drug: Antibacterial therapies

Interventions

Lactoferrin DRUG

antioxidant, immunomodulatory, anti-inflammatory, antimicrobial effect

Lactoferrin

Antioxidant therapies DRUG

Acetyl cysteine 600 mg / 12 hr

Standard

Dexamethasone DRUG

dexamethasone I.V 8 mg / day

Standard

Antibacterial therapies DRUG

Antibacterial drugs in their approved doses

Standard

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• inability to give informed consent by patients or their relative,
• history of hypersensitivity to milk products,
• history of lactoferrin use in the past 6 months,
• patients with lactose intolerance,
• patients with no enteral access to administer LF either orally or by Ryle tube,
• patients who are expected to die within 48 hours, and
• patients with poor oral absorption as in case of shock and resected bowel.

Sponsors & Collaborators

• Mansoura University Hospital: lead

Study Sites (1)

Mansoura University hospital

Al Mansurah, El-dakhlia, Egypt

Location

Related Publications (38)

• Artym J, Kocieba M, Zaczynska E, Adamik B, Kubler A, Zimecki M, Kruzel M. Immunomodulatory properties of human recombinant lactoferrin in mice: Implications for therapeutic use in humans. Adv Clin Exp Med. 2018 Mar;27(3):391-399. doi: 10.17219/acem/68440.

  PMID: 29533543 BACKGROUND

• Hegazy, S.K., Hassan, A.H. The effect of combination treatment with casirivimab and imdevimab versus standard antiviral therapy on clinical outcomes in hospitalized COVID-19 patients. Discov Med 1, 71 (2024). https://doi.org/10.1007/s44337-024-00045-3

  BACKGROUND

• Baker HM, Baker EN. A structural perspective on lactoferrin function. Biochem Cell Biol. 2012 Jun;90(3):320-8. doi: 10.1139/o11-071. Epub 2012 Jan 31.

  PMID: 22292559 BACKGROUND

• Legrand D, Pierce A, Elass E, Carpentier M, Mariller C, Mazurier J. Lactoferrin structure and functions. Adv Exp Med Biol. 2008;606:163-94. doi: 10.1007/978-0-387-74087-4_6.

  PMID: 18183929 BACKGROUND

• Siqueiros-Cendon T, Arevalo-Gallegos S, Iglesias-Figueroa BF, Garcia-Montoya IA, Salazar-Martinez J, Rascon-Cruz Q. Immunomodulatory effects of lactoferrin. Acta Pharmacol Sin. 2014 May;35(5):557-66. doi: 10.1038/aps.2013.200.

  PMID: 24786230 BACKGROUND

• Bukowska-Osko I, Popiel M, Kowalczyk P. The Immunological Role of the Placenta in SARS-CoV-2 Infection-Viral Transmission, Immune Regulation, and Lactoferrin Activity. Int J Mol Sci. 2021 May 28;22(11):5799. doi: 10.3390/ijms22115799.

  PMID: 34071527 BACKGROUND

• Kowalczyk P, Kaczynska K, Kleczkowska P, Bukowska-Osko I, Kramkowski K, Sulejczak D. The Lactoferrin Phenomenon-A Miracle Molecule. Molecules. 2022 May 4;27(9):2941. doi: 10.3390/molecules27092941.

  PMID: 35566292 BACKGROUND

• Poljsak B, Suput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev. 2013;2013:956792. doi: 10.1155/2013/956792. Epub 2013 Apr 29.

  PMID: 23738047 BACKGROUND

• Kowalczyk P, Sulejczak D, Kleczkowska P, Bukowska-Osko I, Kucia M, Popiel M, Wietrak E, Kramkowski K, Wrzosek K, Kaczynska K. Mitochondrial Oxidative Stress-A Causative Factor and Therapeutic Target in Many Diseases. Int J Mol Sci. 2021 Dec 13;22(24):13384. doi: 10.3390/ijms222413384.

  PMID: 34948180 BACKGROUND

• Parekattil S.J., Esteves S.C., Agarwal A. Male Infertility. Springer; Berlin/Heidelberg, Germany: 2020. Harmful Effects of Antioxidant Therapy

  BACKGROUND

• Abdelhamid M, Jung CG, Zhou C, Abdullah M, Nakano M, Wakabayashi H, Abe F, Michikawa M. Dietary Lactoferrin Supplementation Prevents Memory Impairment and Reduces Amyloid-beta Generation in J20 Mice. J Alzheimers Dis. 2020;74(1):245-259. doi: 10.3233/JAD-191181.

  PMID: 31985470 BACKGROUND

• Shi P, Fan F, Chen H, Xu Z, Cheng S, Lu W, Du M. A bovine lactoferrin-derived peptide induced osteogenesis via regulation of osteoblast proliferation and differentiation. J Dairy Sci. 2020 May;103(5):3950-3960. doi: 10.3168/jds.2019-17425. Epub 2020 Mar 18.

  PMID: 32197844 BACKGROUND

• Moreno-Navarrete JM, Ortega FJ, Bassols J, Ricart W, Fernandez-Real JM. Decreased circulating lactoferrin in insulin resistance and altered glucose tolerance as a possible marker of neutrophil dysfunction in type 2 diabetes. J Clin Endocrinol Metab. 2009 Oct;94(10):4036-44. doi: 10.1210/jc.2009-0215. Epub 2009 Jul 7.

  PMID: 19584176 BACKGROUND

• Kaczmarek N, Jamka M, Walkowiak J. [An association of selected polymorphisms of the lactoferrin gene and genes for lactoferrin receptors in the prevalence of metabolic disorders in obese subjects]. Pol Merkur Lekarski. 2020 Apr 22;48(284):120-123. Polish.

  PMID: 32352945 BACKGROUND

• Ikeda Y, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Yoshida S, Aihara K, Tsuchiya K, Tamaki T. Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia. J Cardiovasc Pharmacol. 2013 May;61(5):423-9. doi: 10.1097/FJC.0b013e318287d526.

  PMID: 23364610 BACKGROUND

• Jenssen H, Hancock RE. Antimicrobial properties of lactoferrin. Biochimie. 2009 Jan;91(1):19-29. doi: 10.1016/j.biochi.2008.05.015. Epub 2008 Jun 5.

  PMID: 18573312 BACKGROUND

• Artym J, Zimecki M. Milk-derived proteins and peptides in clinical trials. Postepy Hig Med Dosw (Online). 2013 Aug 6;67:800-16. doi: 10.5604/17322693.1061635.

  PMID: 24018446 BACKGROUND

• Tolone S, Pellino V, Vitaliti G, Lanzafame A, Tolone C. Evaluation of Helicobacter Pylori eradication in pediatric patients by triple therapy plus lactoferrin and probiotics compared to triple therapy alone. Ital J Pediatr. 2012 Oct 31;38:63. doi: 10.1186/1824-7288-38-63.

  PMID: 23114016 BACKGROUND

• Wu J, Chen J, Wu W, Shi J, Zhong Y, van Tol EA, Tang Q, Cai W. Enteral supplementation of bovine lactoferrin improves gut barrier function in rats after massive bowel resection. Br J Nutr. 2014 Aug 28;112(4):486-92. doi: 10.1017/S000711451400107X. Epub 2014 May 15.

  PMID: 24830343 BACKGROUND

• Sherman MP, Sherman J, Arcinue R, Niklas V. Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants. J Pediatr. 2016 Jun;173 Suppl:S37-42. doi: 10.1016/j.jpeds.2016.02.074.

  PMID: 27234409 BACKGROUND

• Berlutti F, Pantanella F, Natalizi T, Frioni A, Paesano R, Polimeni A, Valenti P. Antiviral properties of lactoferrin--a natural immunity molecule. Molecules. 2011 Aug 16;16(8):6992-7018. doi: 10.3390/molecules16086992.

  PMID: 21847071 BACKGROUND

• Miotto M, Di Rienzo L, Bo L, Boffi A, Ruocco G, Milanetti E. Molecular Mechanisms Behind Anti SARS-CoV-2 Action of Lactoferrin. Front Mol Biosci. 2021 Feb 15;8:607443. doi: 10.3389/fmolb.2021.607443. eCollection 2021.

  PMID: 33659275 BACKGROUND

• Manzoni P, Stolfi I, Messner H, Cattani S, Laforgia N, Romeo MG, Bollani L, Rinaldi M, Gallo E, Quercia M, Maule M, Mostert M, Decembrino L, Magaldi R, Mosca F, Vagnarelli F, Memo L, Betta PM, Stronati M, Farina D; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections-the Italian Society of Neonatology. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. Pediatrics. 2012 Jan;129(1):116-23. doi: 10.1542/peds.2011-0279. Epub 2011 Dec 19.

  PMID: 22184648 BACKGROUND

• León-Sicairos N., Ordaz-Pichardo C., Carrero J.C., de la Garza M. Natural Remedies in the Fight Against Parasites. Intechopen; London, UK: 2017. Lactoferrin in the Battle against Intestinal Parasites: A Review.

  BACKGROUND

• Yamauchi K, Wakabayashi H, Shin K, Takase M. Bovine lactoferrin: benefits and mechanism of action against infections. Biochem Cell Biol. 2006 Jun;84(3):291-6. doi: 10.1139/o06-054.

  PMID: 16936799 BACKGROUND

• Alexander DB, Iigo M, Abdelgied M, Ozeki K, Tanida S, Joh T, Takahashi S, Tsuda H. Bovine lactoferrin and Crohn's disease: a case study. Biochem Cell Biol. 2017 Feb;95(1):133-141. doi: 10.1139/bcb-2016-0107. Epub 2016 Nov 30.

  PMID: 28165294 BACKGROUND

• He S, McEuen AR, Blewett SA, Li P, Buckley MG, Leufkens P, Walls AF. The inhibition of mast cell activation by neutrophil lactoferrin: uptake by mast cells and interaction with tryptase, chymase and cathepsin G. Biochem Pharmacol. 2003 Mar 15;65(6):1007-15. doi: 10.1016/s0006-2952(02)01651-9.

  PMID: 12623133 BACKGROUND

• Wakabayashi H, Yamauchi K, Abe F. Quality control of commercial bovine lactoferrin. Biometals. 2018 Jun;31(3):313-319. doi: 10.1007/s10534-018-0098-2. Epub 2018 Apr 4.

  PMID: 29619653 BACKGROUND

• Nappi C, Tommaselli GA, Morra I, Massaro M, Formisano C, Di Carlo C. Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study. Acta Obstet Gynecol Scand. 2009;88(9):1031-5. doi: 10.1080/00016340903117994.

  PMID: 19639462 BACKGROUND

• Chang R, Ng TB, Sun WZ. Lactoferrin as potential preventative and adjunct treatment for COVID-19. Int J Antimicrob Agents. 2020 Sep;56(3):106118. doi: 10.1016/j.ijantimicag.2020.106118. Epub 2020 Jul 30.

  PMID: 32738305 BACKGROUND

• Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998 Nov;26(11):1793-800. doi: 10.1097/00003246-199811000-00016.

  PMID: 9824069 BACKGROUND

• Eltahan NH, Elsawy NH, Abdelaaty KM, Elhamaky AS, Hassan AH, Emara MM. Atorvastatin for reduction of 28-day mortality in severe and critical COVID-19 patients: a randomized controlled trial. Respir Res. 2024 Feb 22;25(1):97. doi: 10.1186/s12931-024-02732-2.

  PMID: 38389078 BACKGROUND

• Hegazy SK, Tharwat S, Hassan AH. Clinical study to compare the efficacy and safety of casirivimab & imdevimab, remdesivir, and favipravir in hospitalized COVID-19 patients. J Clin Virol Plus. 2023 Jun;3(2):100151. doi: 10.1016/j.jcvp.2023.100151. Epub 2023 May 10.

  PMID: 37220480 BACKGROUND

• Hegazy SK, Tharwat S, Hassan AH. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients. Open Med (Wars). 2023 Aug 9;18(1):20230768. doi: 10.1515/med-2023-0768. eCollection 2023.

  PMID: 37588660 BACKGROUND

• Hegazy SK, Tharwat S, Hassan AH. Comparing the efficacy of regen-cov, remdesivir, and favipiravir in reducing invasive mechanical ventilation need in hospitalized COVID-19 patients. World J Clin Cases. 2023 Sep 16;11(26):6105-6121. doi: 10.12998/wjcc.v11.i26.6105.

  PMID: 37731581 BACKGROUND

• Hegazy SK, Hassan AH. Comparing the Efficacy of Remdesivir, Favipiravir, and Casirivimab and Imdevimab on Duration of Hospitalization and ICU Stay of Hospitalized COVID-19 Patients. Life Science Research Communications; 2024; 1(1),21-30. Available at: https://doi.org/10.5530/lsrc.1.1.7

  BACKGROUND

• Hassan AH, Hegazy SK, Radwan ST. Clinical Study to Evaluate the Possible Efficacy and Safety of Antibodies Combination (casirivimab and imdevimab) versus standard antiviral therapy as antiviral agent against Corona virus 2 infection in hospitalized COVID-19 patients. medRxiv. 2022. (preprint). Available from: doi: 10.1101/2022.08.20.22279020

  BACKGROUND

• Hassan AH, Hegazy SK, Radwan ST. Clinical Study to Evaluate the Possible Efficacy and Safety of Antibodies Combination (casirivimab and imdevimab) versus standard antiviral therapy as antiviral agent against Corona virus 2 infection in hospitalized COVID-19 patients. Research Square; 2023. Available from: doi: 10.21203/rs.3.rs-1991618/v2.

  BACKGROUND

Related Links

• Study data

MeSH Terms

Conditions

Critical Illness

Interventions

Lactoferrin; Dexamethasone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Glycoproteins; Glycoconjugates; Carbohydrates; Transferrins; Iron-Binding Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Lactoglobulins; Whey Proteins; Milk Proteins; Animal Proteins, Dietary; Dietary Proteins; Globulins; Metalloproteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ahmed H Hassan, Pharmacist

  Mansoura University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahmed H Hassan, Pharmacist

CONTACT

+201554658010; ahmedony26@gmail.com

Ahmed H Hassan, Pharmacist

CONTACT

+201155848245; ahmedony26@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 7, 2023
• Study Start: December 29, 2025
• Primary Completion (Estimated): December 29, 2027
• Study Completion (Estimated): December 29, 2027
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After the end and publication of the study
• Access Criteria: all will be accessible

Locations

EG (1)