KeratoconusPhase 2NCT02514200
Treatment of Keratoconus With Advanced CXL-II
A Phase 2 study testing Topography-based CXL (KXL2), Conventional pulsed CXL (pCXL) and Riboflavin in people with Keratoconus, run by Umeå University.
Trial summary
The purpose of this study is to determine whether individualized, topography-based corneal crosslinking for keratoconus can improve the optical outcomes of the treatment. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Keratoconus
- What is being tested?
- Topography-based CXL (KXL2), Conventional pulsed CXL (pCXL) and Riboflavin
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Mar 2014to Oct 2019
- Phase
- Phase 2
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients planned for corneal crosslinking.
- Uni-or bilateral keratoconus diagnosis based on the Amsler-Krumeich grading and the "Total Deviation" keratoconus quantification value from the "Belin-Ambrosio enhanced ectasia" measurements of the Pentacam HR® Scheimpflug camera, and an altered red reflex and/or an irregular cornea seen as distortion of the keratometric mires.
- Progression of the keratoconus in the eye in question, documented with Scheimpflug photography using the Oculus Pentacam HR® Scheimpflug camera and/or repeated subjective refraction and keratometry.
- Minimum corneal thickness of 400 μm at the thinnest point after epithelial removal.
- ≥12 years of age
- No ocular abnormalities except keratoconus
- No previous ocular surgery
- No cognitive insufficiency interfering with the informed consent.
Who cannot join
- Age under 12
- Any corneal abnormalities except keratoconus
- Previous ocular surgery
- Cognitive insufficiency
About this study
Official title: Treatment of Keratoconus With Advanced Corneal Crosslinking-II
The purpose of this study is to determine whether individualized, topography-based corneal crosslinking for keratoconus can improve the optical outcomes of the treatment.
Read the detailed description
The study is designed as a prospective, open label, randomized controlled trial involving patients aged 12 years or older of both genders with uni- or bilateral keratoconus planned for routine corneal crosslinking (CXL) at the Department of Clinical Sciences / Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study involves 25+25 eyes with keratoconus, which are randomized to receive either conventional pulsed crosslinking with a uniform, universal 8 mm treatment pattern of 5.4 J/cm2 (pCXL; n=25), or a modified treatment - individualized topography-based corneal crosslinking (KXL2; n=25). In the latter treatment zone has an individualized arcuate shape and spares a 2 mm central optical zone. The size of the treatment zone is based on Pentacam HR® corneal tomography, and is determined by the transition zone where the corneal curvature drops off by ≥2D. The energy distribution is based on the maximum corneal steepness (Kmax) value retrieved from the Pentacam HR® tomography: ≤47.0D - 7.2 J/cm2; 47.1-52.0D - 10 J/cm2; ≥52.1D - 15 J/cm2. Thus, the thin protruding areas of the cornea are crosslinked, whereas the parts with a more normal shape are not. The aim is to potentially improve the optical outcome after the treatment.
Patients are randomized to either of the two treatment arms utilizing a computer list of unique random numbers between 1 and 50; an even number will be treated with KXL2 and an uneven number with pCXL. Bilateral inclusion is allowed, and the second eye to be treated will be assigned to the other group, i.e. eye number two will not get the same treatment as eye number 1.
All patients are informed about the procedures and provide oral and written consent before inclusion in the study.
At baseline, before treatment, each eye is evaluated with autorefractometer measurement (Oculus Parc-1®), uncorrected and best spectacle-corrected LogMAR visual acuity, Oculus Pentacam HR® Scheimpflug photography, Oculus CorVis® high-speed Scheimpflug photography, corneal endothelial photography with a specular microscope camera, Goldmann applanation tonometry and biomicroscopy.
For the Pentacam HR® rotating Scheimpflug camera, each eye is photographed using the "25 pictures" program under standardized, mesopic light conditions. Multiple variables will be analyzed, and individual photographs also will be analyzed manually for light backscatter and for the occurrence of a demarcation line, by a masked observer. The corneal biomechanical characteristics are assessed with data from the Oculus CorVis®, and corneal endothelial morphometry, including endothelial cell density is assessed manually and automatically from specular microscopy photographs taken with the Topcon SP-2000 endothelial camera. All investigations are repeated at 1 month, 3 months, 6 months and 12 months after the treatment.
- Conditions
- Keratoconus
- Being tested
- Topography-based CXL (KXL2), Conventional pulsed CXL (pCXL), Riboflavin, Avedro KXL II
- Medical subject headings
- Keratoconus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topography-based CXL (KXL2)Procedure or surgery
The keratoconus cornea is treated with epithelial debridement in local anesthesia, and then soaked in Riboflavin by repeated topical application every 3 minutes during 10 minutes. The cornea is then irradiated with pulsed ultraviolet light (1s on/1s off) in a topography-based arcuate shape with the Avedro KXL2® with an energy from 7.2-15.0 J/cm2 depending on the severity of the keratoconus.
Conventional pulsed CXL (pCXL)Procedure or surgery
The keratoconus cornea is treated with epithelial debridement in local anesthesia, and then soaked in Riboflavin by repeated topical application every 3 minutes during 10 minutes. The cornea is then irradiated with pulsed ultraviolet light (1s on/1s off) in a central round 8mm zone with the Avedro KXL2® with an energy of 5.4 J/cm2.
RiboflavinDrug
Riboflavin is added topically immediately before the treatment every 3 minutes during 10 minutes in the eye to be treated
Avedro KXL IIDevice
The KXL II™ System crosslinking device from Avedro, Inc. is used for ultraviolet irradiation of the cornea after riboflavin application in both treatment arms.
| Study group | Role | What they receive |
|---|---|---|
| Topography-based CXL (KXL2) | Experimental | Individualized pulsed topography-based corneal crosslinking; 1 second on, 1 second off; 7.2J/cm2 - 15.0J/cm2; arcuate treatment zone. The Avedro KXL II™ System is used for the crosslinking after epithelial debridement in topical anesthesia and application of topical riboflavin every 3 minutes for 10 minutes. Receives: Procedure: Topography-based CXL (KXL2); Drug: Riboflavin; Device: Avedro KXL II |
| Conventional pulsed CXL (pCXL) | Active comparator | Conventional pulsed corneal crosslinking; 1 second on, 1 second off; 5.4 J/cm2; 8 mm central treatment zone. The Avedro KXL II™ System is used for the crosslinking after epithelial debridement in topical anesthesia and application of topical riboflavin every 3 minutes for 10 minutes. Receives: Procedure: Conventional pulsed CXL (pCXL); Drug: Riboflavin; Device: Avedro KXL II |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in refraction
Change from baseline in refractive errors, including lower and higher order aberrations in the cornea.
Measured: 1, 3, 6 and 12 months after the treatment
Secondary outcomes (5)
Change from baseline in ETDRS LogMAR visual acuity
Changes from baseline in uncorrected and best spectacle corrected visual acuity assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, graded in logarithmic values of the minimal angle of resolution.
Measured: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal densitometry
Change from baseline in corneal densitometry (corneal light backscatter), assessed with the Oculus Pentacam HR® rotating Scheimpflug camera.
assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, graded in logarithmic values of the minimal angle of resolution.
Measured: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal biomechanical stability measured with GAT
Change from baseline in biomechanical stability assessed with the Goldmann applanation tonometer (GAT).
Measured: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal biomechanical stability measured with CorVis®
Change from baseline in biomechanical stability assessed with the Oculus CorVis high-speed Scheimpflug camera.
Measured: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal endothelial morphometry
Change from baseline in corneal endothelial morphometry, including cell density.
Measured: 1, 3, 6 and 12 months after the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2015 (estimated)
- Study startMar 2014
- Primary completionOct 2019 (estimated)
- Study completionOct 2019 (estimated)
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 KeratoconusStudies of the same condition, open and under way.
- More trials run by Umeå UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02514200
- Sponsor's protocol ID
- KXL2
- Status last verified
- Dec 2017
- First submitted
- 30 Jul 2015
- Last updated
- 16 May 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Nordstrom M, Schiller M, Fredriksson A, Behndig A. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol. 2017 Jul;101(7):920-925. doi: 10.1136/bjophthalmol-2016-309210. Epub 2016 Nov 29.
PubMed 27899371
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Keratoconus With Advanced Corneal Crosslinking-II
- ClinicalTrials.gov ID
- NCT02514200
- Acronym / sponsor ID
- KXL2
- Conditions
- Keratoconus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 3 Aug 2015 (estimated)
- 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.
The purpose of this study is to determine whether individualized, topography-based corneal crosslinking for keratoconus can improve the optical outcomes of the treatment.
Detailed description
The study is designed as a prospective, open label, randomized controlled trial involving patients aged 12 years or older of both genders with uni- or bilateral keratoconus planned for routine corneal crosslinking (CXL) at the Department of Clinical Sciences / Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study involves 25+25 eyes with keratoconus, which are randomized to receive either conventional pulsed crosslinking with a uniform, universal 8 mm treatment pattern of 5.4 J/cm2 (pCXL; n=25), or a modified treatment - individualized topography-based corneal crosslinking (KXL2; n=25). In the latter treatment zone has an individualized arcuate shape and spares a 2 mm central optical zone. The size of the treatment zone is based on Pentacam HR® corneal tomography, and is determined by the transition zone where the corneal curvature drops off by ≥2D. The energy distribution is based on the maximum corneal steepness (Kmax) value retrieved from the Pentacam HR® tomography: ≤47.0D - 7.2 J/cm2; 47.1-52.0D - 10 J/cm2; ≥52.1D - 15 J/cm2. Thus, the thin protruding areas of the cornea are crosslinked, whereas the parts with a more normal shape are not. The aim is to potentially improve the optical outcome after the treatment.
Patients are randomized to either of the two treatment arms utilizing a computer list of unique random numbers between 1 and 50; an even number will be treated with KXL2 and an uneven number with pCXL. Bilateral inclusion is allowed, and the second eye to be treated will be assigned to the other group, i.e. eye number two will not get the same treatment as eye number 1.
All patients are informed about the procedures and provide oral and written consent before inclusion in the study.
At baseline, before treatment, each eye is evaluated with autorefractometer measurement (Oculus Parc-1®), uncorrected and best spectacle-corrected LogMAR visual acuity, Oculus Pentacam HR® Scheimpflug photography, Oculus CorVis® high-speed Scheimpflug photography, corneal endothelial photography with a specular microscope camera, Goldmann applanation tonometry and biomicroscopy.
For the Pentacam HR® rotating Scheimpflug camera, each eye is photographed using the "25 pictures" program under standardized, mesopic light conditions. Multiple variables will be analyzed, and individual photographs also will be analyzed manually for light backscatter and for the occurrence of a demarcation line, by a masked observer. The corneal biomechanical characteristics are assessed with data from the Oculus CorVis®, and corneal endothelial morphometry, including endothelial cell density is assessed manually and automatically from specular microscopy photographs taken with the Topcon SP-2000 endothelial camera. All investigations are repeated at 1 month, 3 months, 6 months and 12 months after the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topography-based CXL (KXL2) | Experimental | Procedure: Topography-based CXL (KXL2), Drug: Riboflavin, Device: Avedro KXL IIIndividualized pulsed topography-based corneal crosslinking; 1 second on, 1 second off; 7.2J/cm2 - 15.0J/cm2; arcuate treatment zone. The Avedro KXL II™ System is used for the crosslinking after epithelial debridement in topical anesthesia and application of topical riboflavin every 3 minutes for 10 minutes. |
| Conventional pulsed CXL (pCXL) | Active comparator | Procedure: Conventional pulsed CXL (pCXL), Drug: Riboflavin, Device: Avedro KXL IIConventional pulsed corneal crosslinking; 1 second on, 1 second off; 5.4 J/cm2; 8 mm central treatment zone. The Avedro KXL II™ System is used for the crosslinking after epithelial debridement in topical anesthesia and application of topical riboflavin every 3 minutes for 10 minutes. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients planned for corneal crosslinking.
- Uni-or bilateral keratoconus diagnosis based on the Amsler-Krumeich grading and the "Total Deviation" keratoconus quantification value from the "Belin-Ambrosio enhanced ectasia" measurements of the Pentacam HR® Scheimpflug camera, and an altered red reflex and/or an irregular cornea seen as distortion of the keratometric mires.
- Progression of the keratoconus in the eye in question, documented with Scheimpflug photography using the Oculus Pentacam HR® Scheimpflug camera and/or repeated subjective refraction and keratometry.
- Minimum corneal thickness of 400 μm at the thinnest point after epithelial removal.
- ≥12 years of age
Key exclusion criteria (4 listed)
- Age under 12
- Any corneal abnormalities except keratoconus
- Previous ocular surgery
- Cognitive insufficiency
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 |
|---|---|---|
| Topography-based CXL (KXL2)The keratoconus cornea is treated with epithelial debridement in local anesthesia, and then soaked in Riboflavin by repeated topical application every 3 minutes during 10 minutes. The cornea is then irradiated with pulsed ultraviolet light (1s on/1s off) in a topography-based arcuate shape with the Avedro KXL2® with an energy from 7.2-15.0 J/cm2 depending on the severity of the keratoconus. | Procedure or surgery | Topography-based CXL (KXL2) |
| Conventional pulsed CXL (pCXL)The keratoconus cornea is treated with epithelial debridement in local anesthesia, and then soaked in Riboflavin by repeated topical application every 3 minutes during 10 minutes. The cornea is then irradiated with pulsed ultraviolet light (1s on/1s off) in a central round 8mm zone with the Avedro KXL2® with an energy of 5.4 J/cm2. | Procedure or surgery | Conventional pulsed CXL (pCXL) |
| RiboflavinRiboflavin is added topically immediately before the treatment every 3 minutes during 10 minutes in the eye to be treated | Drug | Conventional pulsed CXL (pCXL), Topography-based CXL (KXL2) |
| Avedro KXL IIThe KXL II™ System crosslinking device from Avedro, Inc. is used for ultraviolet irradiation of the cornea after riboflavin application in both treatment arms. | Device | Conventional pulsed CXL (pCXL), Topography-based CXL (KXL2) |
Primary outcome
Change from baseline in refraction
Time frame: 1, 3, 6 and 12 months after the treatment
Change from baseline in refractive errors, including lower and higher order aberrations in the cornea.
5 secondary outcomes
Change from baseline in ETDRS LogMAR visual acuity
Time frame: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal densitometry
Time frame: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal biomechanical stability measured with GAT
Time frame: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal biomechanical stability measured with CorVis®
Time frame: 1, 3, 6 and 12 months after the treatment
Change from baseline in corneal endothelial morphometry
Time frame: 1, 3, 6 and 12 months after the treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2018.
- Derived from this study: PubMed 27899371Nordstrom M, Schiller M, Fredriksson A, Behndig A. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol. 2017 Jul;101(7):920-925. doi: 10.1136/bjophthalmol-2016-309210. Epub 2016 Nov 29.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topography-based CXL (KXL2), Conventional pulsed CXL (pCXL) and Riboflavin in people with Keratoconus, run by Umeå University.
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 8 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: status not confirmed, as of the sponsor's last update on 16 May 2018. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Change from baseline in refraction (time frame: 1, 3, 6 and 12 months after the 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 NCT02514200, 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 16 May 2018.