Treatment of Corneal Infiltrates Secondary to Epidemic Keratoconjunctivitis

NCT04376970 | Completed Phase 4 FDA Drug

• 1 other identifier: UR17DN02
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: To compare efficiency and tolerance between topical 0.5% cyclosporine A and fluorometholone in patients with subepithelial corneal infiltrates (SEIs). Methods : A prospective double-blind randomized study was conducted involving 72 eyes, 38 treated with topical fluorometholone and 34 eyes treated with cyclosporine A 0.5% eyedrops, having SEIs. Treatment was considered successful if there was reduction of SEIs and improvement in visual acuity (two snellen lines). Tolerance was mainly evaluated by Schirmer test, conjunctival hyperemia and burning sensation upon eyedrops instillation.

Conditions

Adenoviral Keratoconjunctivitis

Keywords

adenoviral keratoconjunctivitis; corticosteroid; cyclosporine; cornea; subepithelial infiltrates

Outcome Measures

Primary Outcomes (2)

• Mean change from baseline in subepithelial infiltrates number

  The subepithelial infiltrates were counted at baseline and at each control visit.The mean change was then calculated between each two visits. Treatment was considrerd efficient if the subepithelial infiltrates decreased half the baseline number or completely disappeared.

  day 0, Month 1, Month 3, Month 6, Month 7

• Mean change from baseline in Schirmer type 1 value

  The Schirmer value was assessed without local anesthesia. Treatment was considered efficient with a good tolerance when the schirmer type 1 was superior than 5ml/5min.

  day 0, Month 1, Month 3, Month 6, Month 7

Secondary Outcomes (7)

• Mean change from baseline in best corrected visual acuity

  day 0, Month 1, Month 3, Month 6

• Mean change from baseline in spheric equivalent

  day 0, Month 6

• Mean change from baseline in clinical score

  day 0, Month 1, Month 3, Month 6

• Overall satisfaction with treatment subjective evaluation: scale

  Month 7

• Number of participants with burning sensation upon eyedrops instillation

  day 0, Month 1, Month 3, Month 6

Study Arms (2)

Fluorometholone group

ACTIVE COMPARATOR

This group included 38 patients treated with topical fluorometholone 0.1% (FLUCON®) 4 times a day for one month then 3 times a day for one month and 2 times a day for four months.

Drug: FLUCON®

Cyclosporine A group

ACTIVE COMPARATOR

This group included 34 patients treated with cyclosporine A 0.5% eye drops prepared in Ricin oil by the pharmacy of Tunis Military Hospital and prescribed 4 times a day for one month then 3 times a day for one month and 2 times a day for four months.

Drug: Cyclosporine A eye drops 0.5%

Interventions

FLUCON® DRUG

The drug was prescribed monthly according to the predefined regimen. It was not namely specefied in the prescription and was delivered by the hospital pharmacy according to the randomisation list.The subjects were masked to the contents and were instructed to return the empty tubes on monthly visit, wherein 1 pack of topical treatment was provided to them. Neither the patient nor the ophthalmologist knew the allocated treatment. No other medication was allowed during the trial. Duration of the whole regimen was six months. The study included an extra month after the end of the regimen. It was called " wash-out ". Patients who had less than one month of treatment or an uncontrolled treatment side effect or who presented a degenerative iron line were excluded from the rest of the regimen.

Also known as: Fluorometholone

Fluorometholone group

Cyclosporine A eye drops 0.5% DRUG

The same regimen was prescribed for both treatments in order to preserve the double-blind characteristic. Cyclosporine eye drops 0.5%, was prepared from an oral solution of cyclosporine (Sandimmun®) and combined with castor oil, both sterilized by filtration. The preparation was carried out in a pharmacotechnical laboratory where a controlled atmosphere area was dedicated to ophthalmic preparations. The castor oil-Sandimmun® solution mixture is made in a sterile receptacle. After stirring, the mixture is distributed into sterile low density polyethylene bottles. A sterile insert and cap including a tamper-evident seal were placed on each bottle. A content control was then carried out on each batch produced. A sterility test was done on a batch of each day of preparation. Each bottle of each batch is then cleaned, polished, labeled and then packaged in a pre-printed box with an adapted notice. The stability was fixed at 6 months before opening and at 15 days after opening.

Also known as: CsA

Cyclosporine A group

Eligibility Criteria

• Age: 9 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• patients having subepithelial infiltrates following epidemic keratoconjunctivites persisting for 14 days or more

You may not qualify if:

• a past history of glaucoma or other anterior or posterior segment disease or surgery
• a chronic use of topical or systemic medications
• pregnancy,
• contact lens wearers,
• patients who couldn't attend at least two regimen visits

Sponsors & Collaborators

• Military Hospital of Tunis: lead

Study Sites (1)

Military Hospital of Tunis

Tunis, Illinois, Tunisia

Location

Related Publications (5)

• Levinger E, Slomovic A, Sansanayudh W, Bahar I, Slomovic AR. Topical treatment with 1% cyclosporine for subepithelial infiltrates secondary to adenoviral keratoconjunctivitis. Cornea. 2010 Jun;29(6):638-40. doi: 10.1097/ICO.0b013e3181c33034.

  PMID: 20458220 BACKGROUND

• Maychuk DY, Vasil'eva OA, Russu LI, Mezentseva MV. [Clinical and immunological comparisons of therapeutic regimens for corneal infiltrates secondary to adenoviral keratoconjunctivitis]. Vestn Oftalmol. 2015 Jul-Aug;131(4):49-55. doi: 10.17116/oftalma2015131449-55. Russian.

  PMID: 26489119 RESULT

• Reinhard T, Godehardt E, Pfahl HG, Sundmacher R. [Local cyclosporin A in nummuli after keratoconjunctivitis epidemica. A pilot study]. Ophthalmologe. 2000 Nov;97(11):764-8. doi: 10.1007/s003470070025. German.

  PMID: 11130165 RESULT

• Aydin Kurna S, Altun A, Oflaz A, Karatay Arsan A. Evaluation of the impact of persistent subepithelial corneal infiltrations on the visual performance and corneal optical quality after epidemic keratoconjunctivitis. Acta Ophthalmol. 2015 Jun;93(4):377-82. doi: 10.1111/aos.12496. Epub 2014 Jul 6.

  PMID: 25043311 RESULT

• Gouider D, Khallouli A, Maalej A, Yousfi MA, Ksiaa I, Bouguerra C, Ajili F, Khairallah M. Corticosteroids Versus Cyclosporine for Subepithelial Infiltrates Secondary to Epidemic Keratoconjunctivitis: A Prospective Randomized Double-Blind Study. Cornea. 2021 Jun 1;40(6):726-732. doi: 10.1097/ICO.0000000000002589.

  PMID: 33201059 DERIVED

MeSH Terms

Conditions

Corneal Diseases

Interventions

Fluorometholone

Condition Hierarchy (Ancestors)

Eye Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Afef Maalej

  Military Hospital of Tunis

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The allocation sequence of the treatment was generated by chance and concealed until all the study was over and all outcomes were assessed. Consecutive patients with subepithelial infiltrates were randomly allocated to one of the two groups by a parallel assignment (1:1).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Teaching hospital assistant lecturer in ophthalmology and a member in the research committee of the military hospital of Tunis

Study Record Dates

• First Submitted: May 2, 2020
• First Posted: May 6, 2020
• Study Start: April 1, 2017
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: May 7, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)