Clinical Evaluation of Hylo-Dual Versus Patanol in Children With Seasonal Allergic Conjunctivitis

Conjunctivitis, Allergic Clinical Trial

Official title:

Randomized Controlled Trial Comparing Olopatadine 0.1% Ophthalmic Solution With Hylo-Dual Ophthalmic Preparation in Children With Seasonal Allergic Conjunctivitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03186755
• Other study ID #: 2017-1431
• Status: Recruiting
• Phase: Phase 4
• Start date: June 11, 2017
• Est. completion date: December 2024

Study information

• Verified date: October 2022
• Source: St. Justine's Hospital
• Contact: Michael Marchand, MD
• Phone: 514-805-1247
• Email: mic9[@]sympatico.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares the efficacy of Hylo-Dual (Hyaluronic acid 0.05% & Ectoine 2.0%) and Olopatadine (Olopatadine hydrochloride ophthalmic solution 0.1%) in the control of seasonal allergic conjunctivitis in the pediatric population. Half of participants will receive Hylo-Dual, while the other half will receive Olopatadine treatment for 2 months.

Description:

Seasonal allergic conjunctivitis (SAC) is an inflammatory response of the conjunctiva triggered by exposure to seasonal allergens. SAC is the most common form of ocular allergy, with an estimated prevalence of approximately 15 to 20%. The distressing signs (redness, chemosis, eyelid swelling) and symptoms (itching, tearing, redness) of SAC may cause extreme discomfort, with a burden due to the frequency and duration of the disease more than to its seriousness.

Olopatadine hydrochloride ophthalmic solution 0.1% is a topical antiallergic agent that is both an antihistamine with high affinity and selectivity for the histamine H1 receptor and a mast cell stabilizer that inhibits the release of histamine and other proinflammatory mediators from human conjunctival mast cells. The efficacy and tolerability of olopatadine has been demonstrated by several comparative studies in adults and children with seasonal allergic conjunctivitis.

Hylo-Dual eye drops is an approved treatment in Canada for children 6 years and older, containing 0.5mg/ml Sodium Hyaluronate, 20mg/ml Ectoine, a borate buffer and water. Ectoine is a natural substance formed by microorganisms to protect themselves from extreme environments (e.g.: salt lakes or hot geysers). They adapt to these conditions by so-called extremolytes, like ectoine, which are osmoprotective substances stabilizing biological membranes. Ectoine has a strong water-binding capacity, forming a physiologic barrier protecting cell membranes from contact with allergenic substances and against inflammatory responses to environmental stress (such as dehydration, e.g. by hyperosmolar tears, UV radiation or airborne allergens). Additionally, ectoine has a stabilizing effect on the lipid phase of the tear film by increasing its elasticity, which causes it to spread evenly over the eye surface and protects against the excessive evaporation of tears.

To the knowledge of the investigators, no systematic interventional prospective study exists comparing the efficacy of Olopatadine and Hylo-Dual for the treatment of seasonal allergic conjunctivitis in the pediatric population. The research question is to determine if both treatment options are equally effective in this population, therefore providing further clinical pharmacologic data relevant to children.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

• Children of either sex and any race aged 6 to 18 years

• History of seasonal allergic conjunctivitis lasting at least 1 allergy season (including patients with rhinoconjunctivitis and atopic dermatitis)

• Current complaint of itching and conjunctival redness in both eyes

• Positive skin reaction to at least one common local grass pollen, including Gramineae, at screening or in the 12 months before the study

Exclusion Criteria:

• Another previous or ongoing ocular disorder

• Presence of significant corneal involvement

• Sensitivity to any component of the study medications

• Use of medication between 1 week before the study and study completion that could confound the interpretation of results (i.e. antihistamines, corticosteroids, nonsteroidal anti-inflammatory drugs, mast cell stabilizers, topical ocular vasoconstrictors)

• Participation in other pharmacologic studies during the month before the study

• Poor baseline visual acuity (not correctable to = 0.6 logMAR in both eyes)

• Autoimmune disease associated with dry eye syndrome (eg, rheumatoid arthritis)

• Inability to discontinue wearing contact lenses during the study

• Inability to discontinue the use of concomitant medication: immunosuppressive drugs, sulfa- or neomycin-containing antibiotics, antibiotics causing allergic reaction

Related Conditions & MeSH terms

• Conjunctivitis
• Conjunctivitis, Allergic
• Conjunctivitis, Vernal

Intervention

Drug:
• Hyaluronic acid 0.05% & Ectoine 2.0%
Treatment of 1 drop three times a day in both eyes for 8 weeks
• Olopatadine hydrochloride ophthalmic solution 0.1%
Treatment of 1 drop two times a day in both eyes for 8 weeks

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine Hospital	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Michael Marchand, MD	Université de Montréal

Country where clinical trial is conducted

Canada, 

References & Publications (35)

Akil H, Celik F, Ulas F, Kara IS. Dry Eye Syndrome and Allergic Conjunctivitis in the Pediatric Population. Middle East Afr J Ophthalmol. 2015 Oct-Dec;22(4):467-71. doi: 10.4103/0974-9233.167814. — View Citation

Banciu HL, Sorokin DY, Tourova TP, Galinski EA, Muntyan MS, Kuenen JG, Muyzer G. Influence of salts and pH on growth and activity of a novel facultatively alkaliphilic, extremely salt-tolerant, obligately chemolithoautotrophic sufur-oxidizing Gammaproteobacterium Thioalkalibacter halophilus gen. nov., sp. nov. from South-Western Siberian soda lakes. Extremophiles. 2008 May;12(3):391-404. doi: 10.1007/s00792-008-0142-1. Epub 2008 Feb 29. — View Citation

Beblo-Vranesevic K, Galinski EA, Rachel R, Huber H, Rettberg P. Influence of osmotic stress on desiccation and irradiation tolerance of (hyper)-thermophilic microorganisms. Arch Microbiol. 2017 Jan;199(1):17-28. doi: 10.1007/s00203-016-1269-6. Epub 2016 Jul 21. — View Citation

Bestvater T, Louis P, Galinski EA. Heterologous ectoine production in Escherichia coli: by-passing the metabolic bottle-neck. Saline Syst. 2008 Aug 29;4:12. doi: 10.1186/1746-1448-4-12. — View Citation

Bielory L, Lien KW, Bigelsen S. Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis. Drugs. 2005;65(2):215-28. Review. — View Citation

Bielory L. Update on ocular allergy treatment. Expert Opin Pharmacother. 2002 May;3(5):541-53. Review. — View Citation

Brémond-Gignac D, Nischal KK, Mortemousque B, Gajdosova E, Granet DB, Chiambaretta F. Atopic Keratoconjunctivitis in Children: Clinical Features and Diagnosis. Ophthalmology. 2016 Feb;123(2):435-437. doi: 10.1016/j.ophtha.2015.07.012. Epub 2015 Aug 13. — View Citation

Buenger J, Driller H. Ectoin: an effective natural substance to prevent UVA-induced premature photoaging. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):232-7. — View Citation

Chen L, Pi L, Fang J, Chen X, Ke N, Liu Q. High incidence of dry eye in young children with allergic conjunctivitis in Southwest China. Acta Ophthalmol. 2016 Dec;94(8):e727-e730. doi: 10.1111/aos.13093. Epub 2016 May 26. — View Citation

Ciprandi G, Turner D, Gross RD. Double-masked, randomized, parallel-group study comparing olopatadine 0.1% ophthalmic solution with cromolyn sodium 2% and levocabastine 0.05% ophthalmic preparations in children with seasonal allergic conjunctivitis. Curr Ther Res Clin Exp. 2004 Mar;65(2):186-99. doi: 10.1016/S0011-393X(04)90032-X. — View Citation

Condon PI, McEwen CG, Wright M, Mackintosh G, Prescott RJ, McDonald C. Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome. Br J Ophthalmol. 1999 Oct;83(10):1121-4. — View Citation

DeLuise VP, Peterson WS. The use of topical Healon tears in the management of refractory dry-eye syndrome. Ann Ophthalmol. 1984 Sep;16(9):823-4. — View Citation

Dogru M, Gunay M, Celik G, Aktas A. Evaluation of the tear film instability in children with allergic diseases. Cutan Ocul Toxicol. 2016 Mar;35(1):49-52. doi: 10.3109/15569527.2015.1010727. Epub 2015 Feb 19. — View Citation

Dwivedi M, Backers H, Harishchandra RK, Galla HJ. Biophysical investigations of the structure and function of the tear fluid lipid layer and the effect of ectoine. Part A: natural meibomian lipid films. Biochim Biophys Acta. 2014 Oct;1838(10):2708-15. doi: 10.1016/j.bbamem.2014.05.011. Epub 2014 May 17. — View Citation

Dwivedi M, Brinkkötter M, Harishchandra RK, Galla HJ. Biophysical investigations of the structure and function of the tear fluid lipid layers and the effect of ectoine. Part B: artificial lipid films. Biochim Biophys Acta. 2014 Oct;1838(10):2716-27. doi: 10.1016/j.bbamem.2014.05.007. Epub 2014 May 20. — View Citation

Gelardi M, Leo ME, Quaranta VN, Iannuzzi L, Tripodi S, Quaranta N, Canonica GW, Passalacqua G. Clinical characteristics associated with conjunctival inflammation in allergic rhinoconjunctivitis. J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):387-91.e1. doi: 10.1016/j.jaip.2015.01.006. Epub 2015 Jan 26. — View Citation

Gill GW, Frost JK, Miller KA. A new formula for a half-oxidized hematoxylin solution that neither overstains nor requires differentiation. Acta Cytol. 1974 Jul-Aug;18(4):300-11. — View Citation

Harishchandra RK, Wulff S, Lentzen G, Neuhaus T, Galla HJ. The effect of compatible solute ectoines on the structural organization of lipid monolayer and bilayer membranes. Biophys Chem. 2010 Aug;150(1-3):37-46. doi: 10.1016/j.bpc.2010.02.007. Epub 2010 Feb 11. — View Citation

Kam KW, Chen LJ, Wat N, Young AL. Topical Olopatadine in the Treatment of Allergic Conjunctivitis: A Systematic Review and Meta-analysis. Ocul Immunol Inflamm. 2017 Oct;25(5):663-677. doi: 10.3109/09273948.2016.1158282. Epub 2016 May 18. Review. — View Citation

Katelaris CH, Ciprandi G, Missotten L, Turner FD, Bertin D, Berdeaux G; International Olopatadine Study Group. A comparison of the efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and cromolyn sodium 2% ophthalmic solution in seasonal allergic conjunctivitis. Clin Ther. 2002 Oct;24(10):1561-75. — View Citation

Leonardi A. Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20. Review. — View Citation

Leonardi A. Pathophysiology of allergic conjunctivitis. Acta Ophthalmol Scand Suppl. 1999;(228):21-3. Review. — View Citation

McLaurin E, Narvekar A, Gomes P, Adewale A, Torkildsen G. Phase 3 Randomized Double-Masked Study of Efficacy and Safety of Once-Daily 0.77% Olopatadine Hydrochloride Ophthalmic Solution in Subjects With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge Model. Cornea. 2015 Oct;34(10):1245-51. doi: 10.1097/ICO.0000000000000562. — View Citation

Mortemousque B, Bourcier T, Khairallah M, Messaoud R, Brignole-Baudouin F, Renault D, Rebika H, Brémond-Gignac D; Ketotifen Study Group. Comparison of preservative-free ketotifen fumarate and preserved olopatadine hydrochloride eye drops in the treatment of moderate to severe seasonal allergic conjunctivitis. J Fr Ophtalmol. 2014 Jan;37(1):1-8. doi: 10.1016/j.jfo.2013.02.007. Epub 2013 Dec 31. — View Citation

Nebbioso M, Zicari AM, Celani C, Lollobrigida V, Grenga R, Duse M. Pathogenesis of Vernal Keratoconjunctivitis and Associated Factors. Semin Ophthalmol. 2015;30(5-6):340-4. doi: 10.3109/08820538.2013.874483. Epub 2014 Feb 27. — View Citation

Onguchi T, Dogru M, Okada N, Kato NA, Tanaka M, Takano Y, Fukagawa K, Shimazaki J, Tsubota K, Fujishima H. The impact of the onset time of atopic keratoconjunctivitis on the tear function and ocular surface findings. Am J Ophthalmol. 2006 Mar;141(3):569-71. — View Citation

Papa V, Aragona P, Russo S, Di Bella A, Russo P, Milazzo G. Comparison of hypotonic and isotonic solutions containing sodium hyaluronate on the symptomatic treatment of dry eye patients. Ophthalmologica. 2001 Mar-Apr;215(2):124-7. — View Citation

Sánchez-Hernández MC, Montero J, Rondon C, Benitez del Castillo JM, Velázquez E, Herreras JM, Fernández-Parra B, Merayo-Lloves J, Del Cuvillo A, Vega F, Valero A, Panizo C, Montoro J, Matheu V, Lluch-Bernal M, González ML, González R, Dordal MT, Dávila I, Colás C, Campo P, Antón E, Navarro A; SEAIC 2010 Rhinoconjunctivitis Committee; Spanish Group Ocular Surface-GESOC. Consensus document on allergic conjunctivitis (DECA). J Investig Allergol Clin Immunol. 2015;25(2):94-106. — View Citation

Shimmura S, Ono M, Shinozaki K, Toda I, Takamura E, Mashima Y, Tsubota K. Sodium hyaluronate eyedrops in the treatment of dry eyes. Br J Ophthalmol. 1995 Nov;79(11):1007-11. — View Citation

Stuart JC, Linn JG. Dilute sodium hyaluronate (Healon) in the treatment of ocular surface disorders. Ann Ophthalmol. 1985 Mar;17(3):190-2. — View Citation

Torkildsen G, Narvekar A, Bergmann M. Efficacy and safety of olopatadine hydrochloride 0.77% in patients with allergic conjunctivitis using a conjunctival allergen-challenge model. Clin Ophthalmol. 2015 Sep 14;9:1703-13. doi: 10.2147/OPTH.S83263. eCollection 2015. — View Citation

Verin P, Easty DL, Secchi A, Ciprandi G, Partouche P, Nemeth-Wasmer G, Brancato R, Harrisberg CJ, Estivin-Ebrardt C, Coster DJ, Apel AJ, Coroneo MT, Knorr M, Carmichael TR, Kent-Smith BT, Abrantes P, Leonardi A, Cerqueti PM, Modorati G, Martinez M. Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis. Am J Ophthalmol. 2001 Jun;131(6):691-8. — View Citation

Vermeulen J, Mercer M. Comparison of the efficacy and tolerability of topical levocabastine and sodium cromoglycate in the treatment of seasonal allergic rhinoconjunctivitis in children. Pediatr Allergy Immunol. 1994 Nov;5(4):209-13. — View Citation

Villani E, Dello Strologo M, Pichi F, Luccarelli SV, De Cillà S, Serafino M, Nucci P. Dry Eye in Vernal Keratoconjunctivitis: A Cross-Sectional Comparative Study. Medicine (Baltimore). 2015 Oct;94(42):e1648. doi: 10.1097/MD.0000000000001648. — View Citation

Wysenbeek YS, Loya N, Ben Sira I, Ophir I, Ben Shaul Y. The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study. Invest Ophthalmol Vis Sci. 1988 Feb;29(2):194-9. — View Citation

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Signs of conjunctival erythema	Assessed by an ophthalmologist on slit-lamp examination. 9-point scale consisting of 0.5-unit increments from 0 (normal) to 4 (total involvement). Scale based on the Efron scale.	56 days
Secondary	Signs of conjunctival erythema	Assessed by an ophthalmologist on slit-lamp examination. 9-point scale consisting of 0.5-unit increments from 0 (normal) to 4 (total involvement). Scale based on the Efron scale.	7 days, 14 days, 30 days, 42 days
Secondary	Signs of conjunctival chemosis	Assessed by an ophthalmologist on slit-lamp examination. 9-point scale consisting of 0.5-unit increments from 0 (normal) to 4 (total involvement).	7 days, 14 days, 30 days, 42 days, 56 days
Secondary	Signs of eyelid swelling	Assessed by an ophthalmologist on slit-lamp examination. 9-point scale consisting of 0.5-unit increments from 0 (normal) to 4 (total involvement).	7 days, 14 days, 30 days, 42 days, 56 days
Secondary	Symptoms of itching, self-rated	Response to the question, "How often during the last 3 days did your eyes itch enough that you wanted to rub them?" Rated on a 5-point scale.	7 days, 14 days, 30 days, 42 days, 56 days
Secondary	Symptoms of redness, self-rated	Rated by patient or parents on an 11-point scale (VAS - Visual Analog Scale) where 0 = no redness and 10 = the most intense redness imaginable.	7 days, 14 days, 30 days, 42 days, 56 days
Secondary	Physician's Impression Scale ratings (change scores)	Rated on a 6-point scale: 0 = clinical cure, 1 = satisfactory clinical response, 2 = slight clinical improvement, 3 = clinically unchanged, 4 = slightly clinically worse, and 5 = significantly clinically worse.	7 days, 14 days, 30 days, 42 days, 56 days
Secondary	Listing of adverse effects potentially related to the ophthalmic treatment	Based on visual acuity, pupil diameter, intraocular pressure, slit-lamp examination and a dilated fundus examination by an ophthalmologist.	7 days, 14 days, 30 days, 42 days, 56 days