Progressive KeratoconusPhase 4NCT04427956
Corneal Crosslinking Treatment Study
A Phase 4 study testing Corneal crosslinking: CXL (UVA 9mW/cm2), Isotonic riboflavin and Hypotonic riboflavin in people with Progressive Keratoconus, run by Region Skane at 1 site in Sweden.
Trial summary
Three different protocols for inducing corneal crosslinks in subjets with progressive keratoconus will be evaluated in this randomised clinical study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Progressive Keratoconus
- What is being tested?
- Corneal crosslinking: CXL (UVA 9mW/cm2), Isotonic riboflavin and Hypotonic riboflavin
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteSweden
- Study dates
- 23 May 2017to 19 Nov 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Progress in keratoconic eye. We define progress as an increase in Kmax of 1.0 diopter in 1 year or 0.5 diopter in 6 months. This increase in Kmax will be accepted as progression if concomitant changes tomographic parameters.
Who cannot join
- Concurrent ocular infection or corneal disease other than keratoconus.
- Pregnancy.
- Treatment with Isotretinoin.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Randomised Corneal Crosslinking Study
Three different protocols for inducing corneal crosslinks in subjets with progressive keratoconus will be evaluated in this randomised clinical study.
Read the detailed description
Riboflavin does not penetrate the intact corneal epithelium. Corneal cross linking (CXL) is typically performed using the so-called "Dresden protocol". The Dresden protocol states 30 minutes of UVA-radiation (3mW/cm2) but a 10 minute irradiation protocol (9mW/cm2) is frequently used. Both of the protocols involve mechanical removal of the epithelium over the central 8 mm of the corneal surface. The first days after treatment therefore involves some degree of pain, often intense, and the presence of a healing epithelial defect may be associated with development of infiltrates in the cornea. A number of approaches have been evaluated in order to promote riboflavin penetration through the intact epithelium, of which iontophoresis appears most promising. Keratoconic corneas are thin at the cone location and sometimes it is difficult to maintain the safety margin of 400 microns during corneal crosslinking. Instead of using isotonic standard riboflavin, a swelling effect of the cornea can be obtained by using hypotonic riboflavin. However, the latter has been indicated as less effective in the process of inducing cross links.
Eighty-one of 81 patients of various degrees of keratoconus will be randomised to one of the following groups: 1) CXL (UVA 9mW/cm2) using isotonic riboflavin, or 2) CXL (UVA 9mW/cm2) using hypotonic riboflavin or 3) Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).
Hypothesis:
- CXL with hypotonic riboflavin or CXL with Ricrolin administered by iontophoresis or CXL with isotonic riboflavin is non-inferior compared to standard CXL with isotonic riboflavin. ii) The morphological structure post-CXL in the three different groups will be similar without any significant differences.
The iontophoresis-assisted treatment arm has been interrupted due to low efficacy in halting disease progression. The results have been published.
- Conditions
- Progressive Keratoconus
- Being tested
- Corneal crosslinking: CXL (UVA 9mW/cm2), Isotonic riboflavin, Hypotonic riboflavin, Iontophoresis
- Keywords
- corneal crosslinking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Corneal crosslinking: CXL (UVA 9mW/cm2)Procedure or surgery
CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.
Isotonic riboflavinDrug
CXL protocol with isotonic riboflavin
Hypotonic riboflavinDrug
CXL protocol with hypotonic riboflavin
IontophoresisProcedure or surgery
CXL protocol with iontophoresis and ricrolin
| Study group | Role | What they receive |
|---|---|---|
| Isotonic riboflavin | Active comparator | CXL (UVA 9mW/cm2) treatment using isotonic riboflavin Receives: Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); Drug: Isotonic riboflavin |
| Hypotonic riboflavin | Active comparator | CXL (UVA 9mW/cm2) using hypotonic riboflavin Receives: Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); Drug: Hypotonic riboflavin |
| Iontophoresis | Active comparator | Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2). Receives: Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2); Procedure: Iontophoresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative change in visual acuity
Uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity (BSCVA)
Measured: Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Postoperative change in Kmax
Maximum corneal steepness
Measured: Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Secondary outcomes (6)
Postoperative change in astigmatism
Corneal astigmatism
Measured: Patients will be evaluated 1, 6, 12 and 24 months after treatment.
postoperative change in corneal nerve cell density
Corneal nerve cell density will be evaluated using confocal microscopy
Measured: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in Keratocyte cell density
Keratocyte cell density will be evaluated using confocal microscopy
Measured: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in endothelial cell count
Endothelial cell count will be evaluated using confocal microscopy
Measured: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in demarcation lines
Identification of the demarcation lines with confocal microscopy will help establishing how deep was the effect of the CXL treatment.
Measured: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in the corneal thickness during CXL treatment
Corneal pachymetry is the process of measuring the thickness of the cornea
Measured: Corneal pachymetry will be evaluated before and then every 5 minutes during 30 minutes under CXL treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start23 May 2017
- Primary completion19 Nov 2024
- Study completion19 Nov 2024
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 Progressive KeratoconusStudies 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
- Model description
- Prospective randomized interventional clinical trial
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ingemar Gustafsson, MD, Principal investigator, Region Skane
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04427956
- Sponsor's protocol ID
- DNR2015/373
- Status last verified
- Jul 2024
- First submitted
- 3 Jun 2020
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gustafsson I, Ivarsen A, Hjortdal J. Early findings in a prospective randomised study on three cross-linking treatment protocols: interruption of the iontophoresis treatment protocol. BMJ Open Ophthalmol. 2023 Sep;8(1):e001406. doi: 10.1136/bmjophth-2023-001406.
PubMed 37739426
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomised Corneal Crosslinking Study
- ClinicalTrials.gov ID
- NCT04427956
- Acronym / sponsor ID
- DNR2015/373
- Conditions
- Progressive Keratoconus
- Keywords
- corneal crosslinking
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Study start
- 23 May 2017 (actual)
- Primary completion
- 19 Nov 2024 (actual)
- Study completion
- 19 Nov 2024 (actual)
- First posted
- 11 Jun 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.
Three different protocols for inducing corneal crosslinks in subjets with progressive keratoconus will be evaluated in this randomised clinical study.
Detailed description
Riboflavin does not penetrate the intact corneal epithelium. Corneal cross linking (CXL) is typically performed using the so-called "Dresden protocol". The Dresden protocol states 30 minutes of UVA-radiation (3mW/cm2) but a 10 minute irradiation protocol (9mW/cm2) is frequently used. Both of the protocols involve mechanical removal of the epithelium over the central 8 mm of the corneal surface. The first days after treatment therefore involves some degree of pain, often intense, and the presence of a healing epithelial defect may be associated with development of infiltrates in the cornea. A number of approaches have been evaluated in order to promote riboflavin penetration through the intact epithelium, of which iontophoresis appears most promising. Keratoconic corneas are thin at the cone location and sometimes it is difficult to maintain the safety margin of 400 microns during corneal crosslinking. Instead of using isotonic standard riboflavin, a swelling effect of the cornea can be obtained by using hypotonic riboflavin. However, the latter has been indicated as less effective in the process of inducing cross links.
Eighty-one of 81 patients of various degrees of keratoconus will be randomised to one of the following groups: 1) CXL (UVA 9mW/cm2) using isotonic riboflavin, or 2) CXL (UVA 9mW/cm2) using hypotonic riboflavin or 3) Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).
Hypothesis:
- CXL with hypotonic riboflavin or CXL with Ricrolin administered by iontophoresis or CXL with isotonic riboflavin is non-inferior compared to standard CXL with isotonic riboflavin. ii) The morphological structure post-CXL in the three different groups will be similar without any significant differences.
The iontophoresis-assisted treatment arm has been interrupted due to low efficacy in halting disease progression. The results have been published.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Prospective randomized interventional clinical trial
| Arm | Type | Receives |
|---|---|---|
| Isotonic riboflavin | Active comparator | Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2), Drug: Isotonic riboflavinCXL (UVA 9mW/cm2) treatment using isotonic riboflavin |
| Hypotonic riboflavin | Active comparator | Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2), Drug: Hypotonic riboflavinCXL (UVA 9mW/cm2) using hypotonic riboflavin |
| Iontophoresis | Active comparator | Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2), Procedure: IontophoresisIontophoresis with Ricrolin with following CXL (UVA 9mW/cm2). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Progress in keratoconic eye. We define progress as an increase in Kmax of 1.0 diopter in 1 year or 0.5 diopter in 6 months. This increase in Kmax will be accepted as progression if concomitant changes tomographic parameters.
Key exclusion criteria (3 listed)
- Concurrent ocular infection or corneal disease other than keratoconus.
- Pregnancy.
- Treatment with Isotretinoin.
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 crosslinking: CXL (UVA 9mW/cm2)CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol. | Procedure or surgery | Hypotonic riboflavin, Iontophoresis, Isotonic riboflavin |
| Isotonic riboflavinCXL protocol with isotonic riboflavin | Drug | Isotonic riboflavin |
| Hypotonic riboflavinCXL protocol with hypotonic riboflavin | Drug | Hypotonic riboflavin |
| IontophoresisCXL protocol with iontophoresis and ricrolin | Procedure or surgery | Iontophoresis |
Primary outcome
Postoperative change in visual acuity
Time frame: Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity (BSCVA)
Postoperative change in Kmax
Time frame: Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Maximum corneal steepness
6 secondary outcomes
Postoperative change in astigmatism
Time frame: Patients will be evaluated 1, 6, 12 and 24 months after treatment.
postoperative change in corneal nerve cell density
Time frame: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in Keratocyte cell density
Time frame: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in endothelial cell count
Time frame: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in demarcation lines
Time frame: Confocal microscopy will be performed at 6 and 12 months.
Postoperative change in the corneal thickness during CXL treatment
Time frame: Corneal pachymetry will be evaluated before and then every 5 minutes during 30 minutes under CXL treatment.
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 22 Nov 2024.
- Derived from this study: PubMed 37739426Gustafsson I, Ivarsen A, Hjortdal J. Early findings in a prospective randomised study on three cross-linking treatment protocols: interruption of the iontophoresis treatment protocol. BMJ Open Ophthalmol. 2023 Sep;8(1):e001406. doi: 10.1136/bmjophth-2023-001406.
- Individual participant dataSharing planned: No
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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.
Ingemar Gustafsson, MD principal investigator
Region Skane
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 Corneal crosslinking: CXL (UVA 9mW/cm2), Isotonic riboflavin and Hypotonic riboflavin in people with Progressive Keratoconus, run by Region Skane at 1 site in Sweden.
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 3 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 22 Nov 2024. 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 Sweden. 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?
Postoperative change in visual acuity (time frame: Patients will be evaluated 1, 6, 12 and 24 months after treatment.). 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 NCT04427956, 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 22 Nov 2024.