Lactoferrin Use in ICU Patients

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 compared to control and standard therapy, 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.

Timeline

Start

2025-09-29

Primary completion

2026-07-05

Completion

2026-07-05

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications

No indication recorded.