Adenoviral KeratoconjunctivitisPhase 4NCT04376970
Treatment of Corneal Infiltrates Secondary to Epidemic Keratoconjunctivitis
A Phase 4 study testing FLUCON® and Cyclosporine A eye drops 0.5% in people with Adenoviral Keratoconjunctivitis, run by Military Hospital of Tunis at 1 site in Tunisia.
Trial 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… Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- Adenoviral Keratoconjunctivitis
- What is being tested?
- FLUCON® and Cyclosporine A eye drops 0.5%
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteTunisia
- Study dates
- 1 Apr 2017to 1 Apr 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- patients having subepithelial infiltrates following epidemic keratoconjunctivites persisting for 14 days or more
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Subepithelial Infiltrates Secondary to Epidemic Keratoconjunctivitis: Corticosteroids Versus Cyclosporine Eyedrops: A Randomized Double-blind Study
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.
Read the detailed description
This study was performed on the 72 eyes of 51 patients who were referred to our clinics for epidemic keratoconjunctivitis (EKC).Diagnosis of EKC was based on the constellation of clinical features. The investigators conducted a double-blind randomized prospective parallel trial involving : 38 patients treated with topical fluorometholone and 34 eyes treated with cyclosporine A 0.5% eye drops. Cyclosporine A eye drops were prepared in Ricin oil by the pharmacy of Tunis Military Hospital. The sample size was measured by our research department, to obtain a conclusion of non-inferiority of cyclosporine A compared to fluorometholone in the chronic phase of EKC.
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.The regimen was the same for both treatments in order to preserve the double-blind characteristic : 4 times a day for one month then 3 times a day for one month and 2 times a day for four months.
Patients were examined on admission to the study and one month , three months, six months and seven months after the onset of treatment. The investigators followed a double-masked fashion in all the phases of the study.
Information gathered in M0 included basic demographic information (age and sex), medical and ophtalmological history, involved eye(s) and duration of symptoms in the acute episode. The investigators evaluated and recorded the interval of time between the onset of the infection and the beginning of the trial and called it " pretherapeutic period ". At each visit, SEIs were photo-documented, best corrected visual acuity (converted to mean logarithm of the minimum angle of resolution), spheric equivalent, SEIs number, intraocular pressure (with non contact tonometers), break-up time and Schimer test type 1 and cup/disc score were recorded.
- Conditions
- Adenoviral Keratoconjunctivitis
- Being tested
- FLUCON®, Cyclosporine A eye drops 0.5%
- Keywords
- adenoviral keratoconjunctivitis, corticosteroid, cyclosporine, cornea, subepithelial infiltrates
- Medical subject headings
- Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLUCON®Drug
Also called Fluorometholone
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.
Cyclosporine A eye drops 0.5%Drug
Also called CsA
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cyclosporine A eye drops 0.5% |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: day 0, Month 1, Month 3, Month 6, Month 7
Secondary outcomes (7)
Mean change from baseline in best corrected visual acuity
A gain of two snellen lines from baseline was considered a mark of treatment efficiency.
Measured: day 0, Month 1, Month 3, Month 6
Mean change from baseline in spheric equivalent
Spheric equivalent was calculated using an automatic refraction. An increase from baseline of 0.25 dioptries was considered a mark of treatment efficiency.
Measured: day 0, Month 6
Mean change from baseline in clinical score
These subjective variables : (1) photophobia; (2) Foreign body sensation ; (3) Visual blurring ; (4) tearing and (5) ocular pain were evaluated according to their severity (0 indicated no ; 1, mild ; and 2, severe). The sum of these variables was calculated for each visit and called clinical score.
Measured: day 0, Month 1, Month 3, Month 6
Overall satisfaction with treatment subjective evaluation: scale
For subjective evaluation of the treatment, patients were asked to evaluate in the seventh month their overall satisfaction with treatment on a scale of 0-10. 0 means no satisfaction with the treatment and 10 means an excellent satisfaction with the treatment.
Measured: Month 7
Number of participants with burning sensation upon eyedrops instillation
Burning sensation upon eyedrops instillation was considered as a treatment intolerance mark.
Measured: day 0, Month 1, Month 3, Month 6
Mean change from baseline in intraocular pressure
Intraocular pressure was measured with with non contact tonometers. An increase of 6 mmHg from baseline value was defined as a steroid-induced glaucoma.
Measured: day 0, Month 1, Month 3, Month 6
Number of participants with appearance of lens opacification and corneal ulcer or superinfection
Lens opacification and corneal ulcer or superinfection were considered as a mark of corticosteroid intolerance.
Measured: up to six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2020
- Study start1 Apr 2017
- Primary completion1 Apr 2019
- Study completion1 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Adenoviral KeratoconjunctivitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Military Hospital of Tunis
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asma Khallouli, Military Hospital of Tunis
- Investigators
- Afef Maalej, Study director, Military Hospital of Tunis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04376970
- Sponsor's protocol ID
- UR17DN02
- Status last verified
- May 2020
- First submitted
- 2 May 2020
- Last updated
- 7 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 20458220Maychuk 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.
PubMed 26489119Reinhard 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.
PubMed 11130165Aydin 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.
PubMed 25043311Gouider 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.
PubMed 33201059
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Subepithelial Infiltrates Secondary to Epidemic Keratoconjunctivitis: Corticosteroids Versus Cyclosporine Eyedrops: A Randomized Double-blind Study
- ClinicalTrials.gov ID
- NCT04376970
- Acronym / sponsor ID
- UR17DN02
- Conditions
- Adenoviral Keratoconjunctivitis
- Keywords
- adenoviral keratoconjunctivitis, corticosteroid, cyclosporine, cornea, subepithelial infiltrates
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Military Hospital of TunisUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 1 Apr 2019 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 6 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study was performed on the 72 eyes of 51 patients who were referred to our clinics for epidemic keratoconjunctivitis (EKC).Diagnosis of EKC was based on the constellation of clinical features. The investigators conducted a double-blind randomized prospective parallel trial involving : 38 patients treated with topical fluorometholone and 34 eyes treated with cyclosporine A 0.5% eye drops. Cyclosporine A eye drops were prepared in Ricin oil by the pharmacy of Tunis Military Hospital. The sample size was measured by our research department, to obtain a conclusion of non-inferiority of cyclosporine A compared to fluorometholone in the chronic phase of EKC.
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.The regimen was the same for both treatments in order to preserve the double-blind characteristic : 4 times a day for one month then 3 times a day for one month and 2 times a day for four months.
Patients were examined on admission to the study and one month , three months, six months and seven months after the onset of treatment. The investigators followed a double-masked fashion in all the phases of the study.
Information gathered in M0 included basic demographic information (age and sex), medical and ophtalmological history, involved eye(s) and duration of symptoms in the acute episode. The investigators evaluated and recorded the interval of time between the onset of the infection and the beginning of the trial and called it " pretherapeutic period ". At each visit, SEIs were photo-documented, best corrected visual acuity (converted to mean logarithm of the minimum angle of resolution), spheric equivalent, SEIs number, intraocular pressure (with non contact tonometers), break-up time and Schimer test type 1 and cup/disc score were recorded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluorometholone group | Active comparator | Drug: FLUCON®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. |
| Cyclosporine A group | Active comparator | Drug: Cyclosporine A eye drops 0.5%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. |
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- patients having subepithelial infiltrates following epidemic keratoconjunctivites persisting for 14 days or more
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLUCON®Also: FluorometholoneThe 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. | Drug | Fluorometholone group |
| Cyclosporine A eye drops 0.5%Also: CsAThe 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. | Drug | Cyclosporine A group |
Primary outcome
Mean change from baseline in subepithelial infiltrates number
Time frame: day 0, Month 1, Month 3, Month 6, Month 7
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.
Mean change from baseline in Schirmer type 1 value
Time frame: day 0, Month 1, Month 3, Month 6, Month 7
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.
7 secondary outcomes
Mean change from baseline in best corrected visual acuity
Time frame: day 0, Month 1, Month 3, Month 6
Mean change from baseline in spheric equivalent
Time frame: day 0, Month 6
Mean change from baseline in clinical score
Time frame: day 0, Month 1, Month 3, Month 6
Overall satisfaction with treatment subjective evaluation: scale
Time frame: Month 7
Number of participants with burning sensation upon eyedrops instillation
Time frame: day 0, Month 1, Month 3, Month 6
Mean change from baseline in intraocular pressure
Time frame: day 0, Month 1, Month 3, Month 6
Number of participants with appearance of lens opacification and corneal ulcer or superinfection
Time frame: up to six months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2020.
- Background: PubMed 20458220Levinger 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.
- Results publication: PubMed 26489119Maychuk 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.
- Results publication: PubMed 11130165Reinhard 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.
- Results publication: PubMed 25043311Aydin 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.
- Derived from this study: PubMed 33201059Gouider 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.
- Individual participant dataSharing planned: No
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Active, not recruiting
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Afef Maalej study director
Military Hospital of Tunis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing FLUCON® and Cyclosporine A eye drops 0.5% in people with Adenoviral Keratoconjunctivitis, run by Military Hospital of Tunis at 1 site in Tunisia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tunisia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change from baseline in subepithelial infiltrates number (time frame: day 0, Month 1, Month 3, Month 6, Month 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04376970, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2020.