Losartan for Corneal Fibrosis

NCT07449000 | Recruiting

• 1 other identifier: OF25-00010
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, double-blinded, controlled clinical trial designed to evaluate the efficacy and safety of topical losartan in improving visual acuity, contrast sensitivity and reducing corneal densitometry, corneal aberrations and corneal scarring severity in adult patients with corneal scars of different etiologies. Participants will be randomly assigned to receive either topical losartan 0.8 mg/mL or placebo eyedrops 6 times per day for six months.

Conditions

Corneal Scarring Fibrosis

Keywords

Corneal scar; Corneal scarring; Corneal haze; Corneal opacity; Topical losartan

Outcome Measures

Primary Outcomes (1)

• Change in Best Corrected Visual Acuity (BCVA)

  BCVA measured using ETDRS chart and reported in LogMAR units.

  Baseline to 6 months.

Secondary Outcomes (10)

• Change in Contrast Sensitivity

  Baseline to 6 months.

• Change in Corneal Haze Severity

  Baseline to 6 months.

• Change in Corneal Scar Density

  Baseline to 6 months

• Change in Corneal Scar Area

  Baseline to 6 months.

• Change in corneal aberrations

  Baseline to 6 months.

Study Arms (2)

Topical losartan

ACTIVE COMPARATOR

Drug: Topical Losartan 0.8 mg/ml ophthalmic Solution, one drop applied six times daily for six months

Drug: Topical losartan

Placebo

PLACEBO COMPARATOR

Drug: Balanced saline solution ophthalmic drops, one drop applied six times daily for six months.

Drug: Placebo Control

Interventions

Topical losartan DRUG

Drug: Topical Losartan 0.8 mg/ml ophthalmic solution, one drop applied six times daily for six months.

Topical losartan

Placebo Control DRUG

Drug: Balanced saline solution ophthalmic drops, one drop applied six times daily for six months.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 years or older
• Presence of corneal scar with a duration of at least 1 month
• Corneal scars of any etiology
• Corneal scars with or without corneal neovascularization
• Stable corneal scar without epithelial defect
• No active treatment for the underlying condition for at least 1 month

You may not qualify if:

• Refusal or inability to provide written informed consent
• Presence of corneal epithelial defect or friable epithelium
• Age under 18 years
• Pregnancy
• Known allergy or hypersensitivity to losartan

Sponsors & Collaborators

• Universidad Autonoma de Nuevo Leon: lead

Study Sites (1)

Ophthalmology Department

Monterrey, Nueo Leon, 64460, Mexico

RECRUITING

Related Publications (51)

• COZAAR® (losartan potassium) tablets, for oral use Initial U.S. Approval: 1995 . FDA

  BACKGROUND

• PLM. (n.d.). COZAAR - Comprimidos. Medicamentos PLM. Recuperado el 9 de febrero de 2025, de https://www.medicamentosplm.com/Home/productos/cozaar.comprimidos/128/101/77344/25

  BACKGROUND

• 49. Mauer, M., Zinman, B., Gardiner, R., Suissa, S., Sinaiko, A., Strand, T., Drummond, K., Donnelly, S., Goodyer, P., Gubler, M. C., & Klein, R. (2009). Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes A BS TR AC T. In N Engl J Med (Vol. 361).

  BACKGROUND

• 48. Burnier M, Waeber B, Brunner HR. Clinical pharmacology of the angiotensin II receptor antagonist losartan potassium in healthy subjects. J Hypertens Suppl. 1995 Jul;13(1):S23-8. doi: 10.1097/00004872-199507001-00003. PMID: 18800452.

  BACKGROUND

• Zandbergen, A. A. M., Marinus, ;, Baggen, G. A., Steven, ;, Lamberts, W. J., Bootsma, A. H., Dick De Zeeuw, ;, & Ouwendijk, R. J. T. (2003). Effect of Losartan on Microalbuminuria in Normotensive Patients with Type 2 Diabetes Mellitus A Randomized Clinical Trial Background: Angiotensin-converting enzyme inhibitors have. www.annals.org

  BACKGROUND

• 46. Kubba S, Agarwal SK, Prakash A, Puri V, Babbar R, Anuradha S. Effect of losartan on albuminuria, peripheral and autonomic neuropathy in normotensive microalbuminuric type 2 diabetics. Neurol India. 2003 Sep;51(3):355-8. PMID: 14652437.

  BACKGROUND

• 45. Pucker AD, Frogozo M, Malooley MM, Harthan JS. Point-Counter Point: Treating Corneal Haze with 0.8 mg/mL Topical Losartan. Clinical Insights in Eyecare. 2024;2(5).

  BACKGROUND

• 44. Rodgers EG, Al-Mohtaseb Z, Chen AJ. Topical Losartan for Treating Corneal Haze After Ultraviolet-A/Riboflavin Collagen Cross-Linking. Cornea. 2024 Sep 1;43(9):1165-1170. doi: 10.1097/ICO.0000000000003527. Epub 2024 Mar 22. PMID: 38573840.

  BACKGROUND

• 43. Sampaio, L. P., Hilgert, G. S. L., Shiju, T. M., Murillo, S. E., Santhiago, M. R., & Wilson, S. E. (2022). Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descemet's membrane-endothelial excision in rabbits. Experimental Eye Research, 216. https://doi.org/10.1016/j.exer.2022.108940

  BACKGROUND

• 42. Sampaio, L. P., Villabona-Martinez, V., Shiju, T. M., Santhiago, M. R., & Wilson, S. E. (2023). Topical Losartan Decreases Myofibroblast Generation But Not Corneal Opacity After Surface Blast-Simulating Irregular PTK in Rabbits. Translational Vision Science and Technology, 12(9). https://doi.org/10.1167/tvst.12.9.20

  BACKGROUND

• 41. Sampaio, L. P., Hilgert, G. S. L., Shiju, T. M., Santhiago, M. R., & Wilson, S. E. (2022). Losartan Inhibition of Myofibroblast Generation and Late Haze (Scarring Fibrosis) After PRK in Rabbits. Journal of Refractive Surgery, 38(12), 820-829. https://doi.org/10.3928/1081597X-20221026-03

  BACKGROUND

• 40. Sampaio, L. P., Hilgert, G. S. L., Shiju, T. M., Santhiago, M. R., & Wilson, S. E. (2022). Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury. Translational Vision Science and Technology, 11(7). https://doi.org/10.1167/tvst.11.7.9

  BACKGROUND

• 39. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC 3rd. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med. 2008 Jun 26;358(26):2787-95. doi: 10.1056/NEJMoa0706585. PMID: 18579813; PMCID: PMC2692965.

  BACKGROUND

• 38. Rosenkranz, S. (2004). TGF-β1 and angiotensin networking in cardiac remodeling. In Cardiovascular Research (Vol. 63, Issue 3, pp. 423-432). https://doi.org/10.1016/j.cardiores.2004.04.030

  BACKGROUND

• 37. Gu, L., Zhu, Y., Lee, M., Nguyen, A., Ryujin, N. T., Huang, J. Y., Pandit, S. K., Chamseddine, S., Xiao, L., Mohamed, Y. I., Kaseb, A. O., Karin, M., & Shalapour, S. (2023). Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells. Proceedings of the National Academy of Sciences of the United States of America, 120(19). https://doi.org/10.1073/pnas.2300706120

  BACKGROUND

• 36. Junaid, A., Hostetter, T. H., & Rosenbergt, M. E. (n.d.). Interaction of Angiotensin II and TGF-J31 in the Rat Remnant Kidney. http://journals.lww.com/jasn

  BACKGROUND

• 35. Marcin Dobaczewski, Wei Chen, Nikolaos G. Frangogiannis, Transforming growth factor (TGF)-β signaling in cardiac remodeling, Journal of Molecular and Cellular Cardiology, Volume 51, Issue 4, 2011,

  BACKGROUND

• 34. Chen, X., Lu, H., Rateri, D. L., Cassis, L. A., & Daugherty, A. (2013). Conundrum of angiotensin II and TGF-β interactions in aortic aneurysms. In Current Opinion in Pharmacology (Vol. 13, Issue 2, pp. 180-185). https://doi.org/10.1016/j.coph.2013.01.002

  BACKGROUND

• 33. Murphy, A. M., Wong, A. L., & Bezuhly, M. (2015). Modulation of angiotensin II signaling in the prevention of fibrosis. In Fibrogenesis and Tissue Repair (Vol. 8, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13069-015-0023-z

  BACKGROUND

• 32. Marcin Dobaczewski, Wei Chen, Nikolaos G. Frangogiannis, Transforming growth factor (TGF)-β signaling in cardiac remodeling, Journal of Molecular and Cellular Cardiology, Volume 51, Issue 4, 2011,

  BACKGROUND

• 31. Chen, X., Lu, H., Rateri, D. L., Cassis, L. A., & Daugherty, A. (2013). Conundrum of angiotensin II and TGF-β interactions in aortic aneurysms. In Current Opinion in Pharmacology (Vol. 13, Issue 2, pp. 180-185). https://doi.org/10.1016/j.coph.2013.01.002

  BACKGROUND

• 30. Murphy, A. M., Wong, A. L., & Bezuhly, M. (2015). Modulation of angiotensin II signaling in the prevention of fibrosis. In Fibrogenesis and Tissue Repair (Vol. 8, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13069-015-0023-z

  BACKGROUND

• 29. Wilson, S. E. (2023). Topical Losartan: Practical Guidance for Clinical Trials in the Prevention and Treatment of Corneal Scarring Fibrosis and Other Eye Diseases and Disorders. In Journal of Ocular Pharmacology and Therapeutics (Vol. 39, Issue 3, pp. 191-206). Mary Ann Liebert Inc. https://doi.org/10.1089/jop.2022.0174

  BACKGROUND

• 28. Pereira-Souza, A. L., Ambrósio, R., Bandeira, F., Salomão, M. Q., Lima, A. S., & Wilson, S. E. (2022). Topical Losartan for Treating Corneal Fibrosis (Haze): First Clinical Experience. Journal of Refractive Surgery, 38(11), 741-746. https://doi.org/10.3928/1081597X-20221018-02

  BACKGROUND

• 27. Chung, J.-H., Kang, Y.-G., Kim, H.-J., Chung, J.-H., Kang, Y.-G., & Kim, H.-J. (1998). Effect of 0.1% dexamethasone on epithelial healing in experimental corneal alkali wounds: morphological changes during the repair process. In Arch Clin Exp Ophthalmol (Vol. 236). Springer-Verlag.

  BACKGROUND

• 26. Mifflin, M. D., Betts, B. S., Frederick, P. A., Feuerman, J. M., Fenzl, C. R., Moshirfar, M., & Zaugg, B. (2017). Efficacy and safety of a 3-month loteprednol etabonate 0.5% gel taper for routine prophylaxis after photorefractive keratectomy compared to a 3-month prednisolone acetate 1% and fluorometholone 0.1% taper. Clinical Ophthalmology, 11, 1113-1118. https://doi.org/10.2147/OPTH.S138272

  BACKGROUND

• 25. Srinivasan, M., Mascarenhas, J., Rajaraman, R., Ravindran, M., Lalitha, P., O'Brien, K. S., Glidden, D. v., Ray, K. J., Oldenburg, C. E., Zegans, M. E., Whitcher, J. P., McLeod, S. D., Porco, T. C., Lietman, T. M., & Acharya, N. R. (2014). The steroids for corneal ulcers trial (SCUT): Secondary 12-month clinical outcomes of a randomized controlled trial. American Journal of Ophthalmology, 157(2). https://doi.org/10.1016/j.ajo.2013.09.025

  BACKGROUND

• 24. Fung, A. T., Tran, T., Lim, L. L., Samarawickrama, C., Arnold, J., Gillies, M., Catt, C., Mitchell, L., Symons, A., Buttery, R., Cottee, L., Tumuluri, K., & Beaumont, P. (2020). Local delivery of corticosteroids in clinical ophthalmology: A review. In Clinical and Experimental Ophthalmology (Vol. 48, Issue 3, pp. 366-401). Blackwell Publishing. https://doi.org/10.1111/ceo.13702

  BACKGROUND

• 23. Mishima, H., Nishida, T., & Otori, T. (n.d.). Dexamethasone Inhibition of Phagocytosis by Corneal Keratocytes in Culture. http://archopht.jamanetwork.com/

  BACKGROUND

• 22. Zhang, T., Wang, X. F., Wang, Z. C., Lou, D., Fang, Q. Q., Hu, Y. Y., Zhao, W. Y., Zhang, L. Y., Wu, L. H., & Tan, W. Q. (2020). Current potential therapeutic strategies targeting the TGF-β/Smad signaling pathway to attenuate keloid and hypertrophic scar formation. In Biomedicine and Pharmacotherapy (Vol. 129). Elsevier Masson s.r.l. https://doi.org/10.1016/j.biopha.2020.110287

  BACKGROUND

• 21. Liu, W., Wang, D. R., & Cao, Y. L. (2004). TGF-β: A Fibrotic Factor in Wound Scarring and a Potential Target for Anti-Scarring Gene Therapy. In Current Gene Therapy (Vol. 4).

  BACKGROUND

• 20. Liu, Y., Li, Y., Li, N. et al. TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21. Sci Rep 6, 32231 (2016). https://doi.org/10.1038/srep32231

  BACKGROUND

• 19. Chen, X., Lu, H., Rateri, D. L., Cassis, L. A., & Daugherty, A. (2013). Conundrum of angiotensin II and TGF-β interactions in aortic aneurysms. In Current Opinion in Pharmacology (Vol. 13, Issue 2, pp. 180-185). https://doi.org/10.1016/j.coph.2013.01.002

  BACKGROUND

• 18. Sampaio, L. P., Martinez, V. V., Shiju, T. M., Hilgert, G. S. L., Santhiago, M. R., & Wilson, S. E. (2023). Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits. Translational Vision Science and Technology, 12(5). https://doi.org/10.1167/tvst.12.5.15

  BACKGROUND

• 17. Jester, J. v., & Ho-Chang, J. (2003). Modulation of cultured corneal keratocyte phenotype by growth factors/cytokines control in vitro contractility and extracellular matrix contraction. Experimental Eye Research, 77(5), 581-592. https://doi.org/10.1016/S0014-4835(03)00188-X

  BACKGROUND

• 16. de Oliveira, R. C., & Wilson, S. E. (2020). Fibrocytes, wound healing, and corneal fibrosis. In Investigative Ophthalmology and Visual Science (Vol. 61, Issue 2). Association for Research in Vision and Ophthalmology Inc. https://doi.org/10.1167/iovs.61.2.28

  BACKGROUND

• 15. Wilson, S. E. (2021). TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs. In Experimental Eye Research (Vol. 207). Academic Press. https://doi.org/10.1016/j.exer.2021.108594

  BACKGROUND

• 14. Hong JW, Liu JJ, Lee JS, et al. Proinflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea. Invest Ophthalmol Vis Sci. 2001;42:2795-2803.

  BACKGROUND

• 13. Kwok, S. S., Shih, K. C., Bu, Y., Lo, A. C. Y., Chan, T. C. Y., Lai, J. S. M., Jhanji, V., & Tong, L. (2019). Systematic Review on Therapeutic Strategies to Minimize Corneal Stromal Scarring after Injury. In Eye and Contact Lens (Vol. 45, Issue 6, pp. 347-355). Lippincott Williams and Wilkins. https://doi.org/10.1097/ICL.0000000000000584

  BACKGROUND

• 12. Wilson, S. E. (2023). The corneal fibroblast: The Dr. Jekyll underappreciated overseer of the responses to stromal injury. Ocular Surface, 29, 53-62. https://doi.org/10.1016/j.jtos.2023.04.012

  BACKGROUND

• 11. de Oliveira, R. C., Tye, G., Sampaio, L. P., Shiju, T. M., DeDreu, J. R., Menko, A. S., Santhiago, M. R., & Wilson, S. E. (2021). TGFβ1 and TGFβ2 proteins in corneas with and without stromal fibrosis: Delayed regeneration of apical epithelial growth factor barrier and the epithelial basement membrane in corneas with stromal fibrosis. Experimental Eye Research, 202. https://doi.org/10.1016/j.exer.2020.108325 13

  BACKGROUND

• 10. Wilson, S. E., Sampaio, L. P., Shiju, T. M., Hilgert, G. S. L., & de Oliveira, R. C. (2022). Corneal Opacity: Cell Biological Determinants of the Transition From Transparency to Transient Haze to Scarring Fibrosis, and Resolution, After Injury. Investigative Ophthalmology and Visual Science, 63(1). https://doi.org/10.1167/iovs.63.1.22

  BACKGROUND

• 9. Flaxman, S. R., Bourne, R. R. A., Resnikoff, S., Ackland, P., Braithwaite, T., Cicinelli, M. v., Das, A., Jonas, J. B., Keeffe, J., Kempen, J., Leasher, J., Limburg, H., Naidoo, K., Pesudovs, K., Silvester, A., Stevens, G. A., Tahhan, N., Wong, T., Taylor, H., … Zheng, Y. (2017). Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. The Lancet Global Health, 5(12), e1221-e1234. https://doi.org/10.1016/S2214-109X(17)30393-5

  BACKGROUND

• 8. Wang, E. Y., Kong, X., Wolle, M., Gasquet, N., Ssekasanvu, J., Mariotti, S. P., Bourne, R., Taylor, H., Resnikoff, S., & West, S. (2023). Global Trends in Blindness and Vision Impairment Resulting from Corneal Opacity 1984-2020: A Meta-analysis. In Ophthalmology (Vol. 130, Issue 8, pp. 863-871). Elsevier Inc. https://doi.org/10.1016/j.ophtha.2023.03.012

  BACKGROUND

• 7. Wilson, S. E. (2023). The Cornea: No Difference in the Wound Healing Response to Injury Related to Whether, or Not, There's a Bowman's Layer. In Biomolecules (Vol. 13, Issue 5). MDPI. https://doi.org/10.3390/biom13050771

  BACKGROUND

• Yam, G. H. F., Riau, A. K., Funderburgh, M. L., Mehta, J. S., & Jhanji, V. (2020). Keratocyte biology. In Experimental Eye Research (Vol. 196). Academic Press. https://doi.org/10.1016/j.exer.2020.108062

  BACKGROUND

• 5. Wilson, S. E., Sampaio, L. P., Shiju, T. M., Hilgert, G. S. L., & de Oliveira, R. C. (2022). Corneal Opacity: Cell Biological Determinants of the Transition From Transparency to Transient Haze to Scarring Fibrosis, and Resolution, After Injury. Investigative Ophthalmology and Visual Science, 63(1). https://doi.org/10.1167/iovs.63.1.22

  BACKGROUND

• 4. Oyster, C. W. (2006). The human eye: Structure and function (2006a ed.). Oxford University Press.

  BACKGROUND

• 3. Sridhar, M. S. (2018). Anatomy of cornea and ocular surface. In Indian Journal of Ophthalmology (Vol. 66, Issue 2, pp. 190-194). Medknow Publications. https://doi.org/10.4103/ijo.IJO_646_17

  BACKGROUND

• 2. Weisenthal, R. W. (2023b). 2023-2024 basic and clinical science courseTM, section 8: External disease and cornea. American Academy of Ophthalmology.

  BACKGROUND

• 1. Meek, K. M., Knupp, C., Lewis, P. N., Morgan, S. R., & Hayes, S. (2024). Structural control of corneal transparency, refractive power and dynamics. In Eye (Basingstoke). Springer Nature. https://doi.org/10.1038/s41433-024-02969-7

  BACKGROUND

MeSH Terms

Conditions

Corneal Injuries; Corneal Opacity

Interventions

Losartan

Condition Hierarchy (Ancestors)

Eye Injuries; Facial Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Corneal Diseases; Eye Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Karim Mohamed-Noriega, Dr. med.

  Universidad Autonoma de Nuevo Leon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karim Mohamed-Noriega, Dr. med.

CONTACT

+52 8113404960; karim.mohamednrg@uanl.edu.mx

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: March 4, 2026
• Study Start: February 12, 2026
• Primary Completion (Estimated): February 11, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 8, 2026

Record last verified: 2026-02

Locations

ME (1)