Infective KeratitisEarly Phase 1NCT06967376
The Role of Adjuvant Corneal Crosslinking in the Management of Infective Keratitis
A Early Phase 1 study testing Corneal Collagen Cross-Linking Solutions and Topical Antimicrobial/Antifungal Medications in people with Infective Keratitis, run by Research Institute of Ophthalmology, Egypt at 2 sites in Egypt.
Trial summary
This was a prospective, single centre, randomised controlled study to evaluate the clinical effectiveness of corneal collagen crosslinking as an adjuvant to antimicrobial therapy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Infective Keratitis
- What is being tested?
- Corneal Collagen Cross-Linking Solutions and Topical Antimicrobial/Antifungal Medications
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesEgypt
- Study dates
- 21 May 2018to 3 Feb 2022
- Phase
- Early Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients presenting with infectious keratitis
Who cannot join
- Infective keratitis < 1mm from limbus
- Corneal thickness < 350μm
- Previous herpetic eye disease
- Expectant and nursing women
Trial locations and contacts
2 sites in 1 country.
Egypt2 sites
Research Institute of Ophthalmology
Giza, Giza Governorate
Research Institute of Ophthalmology
Giza
About this study
Official title: The Role of Adjuvant Cross Linking in the Management of Infective Keratitis - an OCT Based Assessment Study
This was a prospective, single centre, randomised controlled study to evaluate the clinical effectiveness of corneal collagen crosslinking as an adjuvant to antimicrobial therapy.
Read the detailed description
This randomised controlled study of forty eyes of forty patients was conducted to assess the impact of corneal collagen crosslinking in addition to antimicrobial therapy.
All forty patients presenting with infective keratitis of various aetiologies (bacterial, fungal, acanthamoeba) were screened and then randomly allocated equally to two groups (A and B). Group A patients were to be offered standard targeted anti-microbial therapy whilst group B were offered CXL in addition to the standard targeted anti-microbial therapy.
Patients were evaluated clinically for visual acuity; infection parameters and dimensions were measured on slit lamp and optical coherence tomography. Evaluations were noted at the baseline visit and subsequently on days 7, 14, and day 30 of treatment
- Conditions
- Infective Keratitis
- Being tested
- Corneal Collagen Cross-Linking Solutions, Topical Antimicrobial/Antifungal Medications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Corneal Collagen Cross-Linking SolutionsProcedure or surgery
Topical anaesthesia was achieved using 0.4% benoxinate hydrochloride drops. Epithelium was removed up to 9 mm diameter. Corneal thickness of the area to be treated was measured (without epithelium) aiming for a starting thickness of no less than 350μm. Corneas thicker than 500μm were dehydrated to reduce thickness by using 70% Glycerol drops applied topically at intervals of 2-3 seconds for a total of five minutes. A schematic representation of PACK-CXL protocol is provided in Figure 1. Iso-osmolar riboflavin drops were instilled topically on the cornea at regular intervals of 2 minutes for a total period of 30 minutes. Thickness was also re-measured every 5 min to ensure that it remained below 500µm during instillation of riboflavin. The cornea was illuminated using a UVX, UV-A 365 nm with an irradiance of 3 mW/cm2 for 30 minutes and a total dose of 5.4 J/cm2 during which riboflavin was instilled every 2 min and corneal pachymetry performed every 5 min. PACK-CXL was performed in a 9
Topical Antimicrobial/Antifungal MedicationsDrug
Initial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/ml, fortified ceftazidime eye drops 50 mg/ml hourly, and the antifungal agent itraconazole 100 mg orally twice per day. This regimen was subject to change according to microbiology culture sensitivities and/or results.
| Study group | Role | What they receive |
|---|---|---|
| Arm that take medical treatment only for infective keratitis | Active comparator | On presentation, all pre-existing treatment was stopped for 48 hours and corneal scrapes for direct smears and cultures using blood agar, chocolate agar, thioglycolate broth and sabouraud dextrose agar were done. Initial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/ml, fortified ceftazidime eye drops 50 mg/ml hourly, and the antifungal agent itraconazole 100 mg orally twice per day. This regimen was subject to change according to microbiology culture sensitivities and/or results. Receives: Drug: Topical Antimicrobial/Antifungal Medications |
| Arm of patients take cross linking as an adjuvant treatment to medical treatment | Active comparator | Patients allocated to the PACK-CXL group were assessed and treated by PACK-CXL within 2 days of treatment initiation. Topical anaesthesia was achieved using 0.4% benoxinate hydrochloride drops. Epithelium was removed up to 9 mm diameter. Corneal thickness of the area to be treated was measured (without epithelium) aiming for a starting thickness of no less than 350μm. Corneas thicker than 500μm were dehydrated to reduce thickness by using 70% Glycerol drops applied topically at intervals of 2-3 seconds for a total of five minutes. A schematic representation of PACK-CXL protocol is provided in Figure 1. Iso-osmolar riboflavin drops were instilled topically on the cornea at regular intervals of 2 minutes for a total period of 30 minutes. Thickness was also re-measured every 5 min to ensure that it remained below 500µm during instillation of riboflavin. The cornea was illuminated using a UVX, UV-A 365 nm with an irradiance of 3 mW/cm2 for 30 minutes and a total dose of 5.4 J/cm2 during Receives: Procedure: Corneal Collagen Cross-Linking Solutions |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical response
Ulcer dimensions will be studied on slit lamp and AS-OCT.
Measured: At presentation; and then on day 7, day 14 and day 30 of commencing treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start21 May 2018
- Primary completion11 Nov 2021
- Study completion3 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infective KeratitisStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Methods Study Design: A prospective, single centre, randomised controlled study of forty eyes of forty patients was conducted. The study was approved by local institutional review board (Approval number 109) and adhered to the Declaration of Helsinki. All patients provided informed consent before enrolling and participating in the study. Selection: All patients presenting with infective keratitis were explained about the study and informed consent was sought (CONSORT Diagram). Fifty-three patients were screened against the exclusion criteria and 13 were excluded. The remaining total of 40 patients were allocated equally to two groups (A and B) by process of simple randomisation. Group A patients were to be offered standard targeted anti-microbial therapy whilst group B were offered CXL in addition to the standard targeted anti-microbial therapy.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research Institute of Ophthalmology, Egypt
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06967376
- Sponsor's protocol ID
- RIO Egypt (approval number 109
- Status last verified
- Nov 2024
- First submitted
- 2 Nov 2024
- Last updated
- 13 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Soliman S, Said D, Maqsood S, Naveed H, Hassan M, Atef A, Saif MY, Gatzioufas Z, Elalfy M. The Role of Adjuvant Corneal Cross-linking in the Management of Infectious Keratitis: An OCT-Based Assessment Study. Adv Ther. 2026 Jun 6. doi: 10.1007/s12325-026-03621-4. Online ahead of print.
PubMed 42250077
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Adjuvant Cross Linking in the Management of Infective Keratitis - an OCT Based Assessment Study
- ClinicalTrials.gov ID
- NCT06967376
- Acronym / sponsor ID
- RIO Egypt (approval number 109
- Conditions
- Infective Keratitis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Research Institute of Ophthalmology, EgyptUniversity, hospital or other
- Study start
- 21 May 2018 (actual)
- Primary completion
- 11 Nov 2021 (actual)
- Study completion
- 3 Feb 2022 (actual)
- First posted
- 13 May 2025 (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.
This was a prospective, single centre, randomised controlled study to evaluate the clinical effectiveness of corneal collagen crosslinking as an adjuvant to antimicrobial therapy.
Detailed description
This randomised controlled study of forty eyes of forty patients was conducted to assess the impact of corneal collagen crosslinking in addition to antimicrobial therapy.
All forty patients presenting with infective keratitis of various aetiologies (bacterial, fungal, acanthamoeba) were screened and then randomly allocated equally to two groups (A and B). Group A patients were to be offered standard targeted anti-microbial therapy whilst group B were offered CXL in addition to the standard targeted anti-microbial therapy.
Patients were evaluated clinically for visual acuity; infection parameters and dimensions were measured on slit lamp and optical coherence tomography. Evaluations were noted at the baseline visit and subsequently on days 7, 14, and day 30 of treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Methods Study Design: A prospective, single centre, randomised controlled study of forty eyes of forty patients was conducted. The study was approved by local institutional review board (Approval number 109) and adhered to the Declaration of Helsinki. All patients provided informed consent before enrolling and participating in the study. Selection: All patients presenting with infective keratitis were explained about the study and informed consent was sought (CONSORT Diagram). Fifty-three patients were screened against the exclusion criteria and 13 were excluded. The remaining total of 40 patients were allocated equally to two groups (A and B) by process of simple randomisation. Group A patients were to be offered standard targeted anti-microbial therapy whilst group B were offered CXL in addition to the standard targeted anti-microbial therapy.
| Arm | Type | Receives |
|---|---|---|
| Arm that take medical treatment only for infective keratitis | Active comparator | Drug: Topical Antimicrobial/Antifungal MedicationsOn presentation, all pre-existing treatment was stopped for 48 hours and corneal scrapes for direct smears and cultures using blood agar, chocolate agar, thioglycolate broth and sabouraud dextrose agar were done. Initial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/ml, fortified ceftazidime eye drops 50 mg/ml hourly, and the antifungal agent itraconazole 100 mg orally twice per day. This regimen was subject to change according to microbiology culture sensitivities and/or results. |
| Arm of patients take cross linking as an adjuvant treatment to medical treatment | Active comparator | Procedure: Corneal Collagen Cross-Linking SolutionsPatients allocated to the PACK-CXL group were assessed and treated by PACK-CXL within 2 days of treatment initiation. Topical anaesthesia was achieved using 0.4% benoxinate hydrochloride drops. Epithelium was removed up to 9 mm diameter. Corneal thickness of the area to be treated was measured (without epithelium) aiming for a starting thickness of no less than 350μm. Corneas thicker than 500μm were dehydrated to reduce thickness by using 70% Glycerol drops applied topically at intervals of 2-3 seconds for a total of five minutes. A schematic representation of PACK-CXL protocol is provided in Figure 1. Iso-osmolar riboflavin drops were instilled topically on the cornea at regular intervals of 2 minutes for a total period of 30 minutes. Thickness was also re-measured every 5 min to ensure that it remained below 500µm during instillation of riboflavin. The cornea was illuminated using a UVX, UV-A 365 nm with an irradiance of 3 mW/cm2 for 30 minutes and a total dose of 5.4 J/cm2 during |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Patients presenting with infectious keratitis
Key exclusion criteria (4 listed)
- Infective keratitis < 1mm from limbus
- Corneal thickness < 350μm
- Previous herpetic eye disease
- Expectant and nursing women
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 |
|---|---|---|
| Corneal Collagen Cross-Linking SolutionsTopical anaesthesia was achieved using 0.4% benoxinate hydrochloride drops. Epithelium was removed up to 9 mm diameter. Corneal thickness of the area to be treated was measured (without epithelium) aiming for a starting thickness of no less than 350μm. Corneas thicker than 500μm were dehydrated to reduce thickness by using 70% Glycerol drops applied topically at intervals of 2-3 seconds for a total of five minutes. A schematic representation of PACK-CXL protocol is provided in Figure 1. Iso-osmolar riboflavin drops were instilled topically on the cornea at regular intervals of 2 minutes for a total period of 30 minutes. Thickness was also re-measured every 5 min to ensure that it remained below 500µm during instillation of riboflavin. The cornea was illuminated using a UVX, UV-A 365 nm with an irradiance of 3 mW/cm2 for 30 minutes and a total dose of 5.4 J/cm2 during which riboflavin was instilled every 2 min and corneal pachymetry performed every 5 min. PACK-CXL was performed in a 9 | Procedure or surgery | Arm of patients take cross linking as an adjuvant treatment to medical treatment |
| Topical Antimicrobial/Antifungal MedicationsInitial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/ml, fortified ceftazidime eye drops 50 mg/ml hourly, and the antifungal agent itraconazole 100 mg orally twice per day. This regimen was subject to change according to microbiology culture sensitivities and/or results. | Drug | Arm that take medical treatment only for infective keratitis |
Primary outcome
clinical response
Time frame: At presentation; and then on day 7, day 14 and day 30 of commencing treatment
Ulcer dimensions will be studied on slit lamp and AS-OCT.
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 13 May 2025.
- Derived from this study: PubMed 42250077Soliman S, Said D, Maqsood S, Naveed H, Hassan M, Atef A, Saif MY, Gatzioufas Z, Elalfy M. The Role of Adjuvant Corneal Cross-linking in the Management of Infectious Keratitis: An OCT-Based Assessment Study. Adv Ther. 2026 Jun 6. doi: 10.1007/s12325-026-03621-4. Online ahead of print.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Corneal Collagen Cross-Linking Solutions and Topical Antimicrobial/Antifungal Medications in people with Infective Keratitis, run by Research Institute of Ophthalmology, Egypt at 2 sites in Egypt.
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 4 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 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Egypt. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
clinical response (time frame: At presentation; and then on day 7, day 14 and day 30 of commencing treatment). 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 NCT06967376, which also lists 1 linked publication.
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 13 May 2025.