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Study terminated due to poor patient recruitment
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| Name | Class |
|---|---|
| Region Östergötland | OTHER |
| Linkoeping University | OTHER_GOV |
| Sahlgrenska University Hospital | OTHER |
| Laboratoires Thea |
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The objective of this clinical study is to test the efficacy of CACICOL20® (RGTA OTR 4120) in improving wound healing and nerve regeneration in the anterior cornea, in a patient population undergoing therapeutic laser treatment for corneal dystrophy or recurrent corneal erosions.
Patients undergoing various surgical treatments of the cornea often suffer from a neural deficit, due to nerves being severed or removed completely during surgery. This can result in pain, impaired epithelial wound healing, reduced tear production, symptoms of dry eye, and loss of ocular surface sensitivity/blink reflex. In addition, surgical wound healing can be accompanied by undesirable formation of scar tissue, which can limit postoperative visual acuity. The investigators' prior clinical experience with patients having undergone surgery of the anterior cornea is that neural recovery is slow and incomplete, while in certain situations scar tissue can form and limit the visual recovery.
In this context, CACICOL20®, a regenerative agent approved for use in healing corneal wounds, presents an interesting opportunity for improving postoperative corneal nerve regeneration and a potentially more rapid restoration of the extracellular matrix environment postoperatively, which can lead to improved neural and visual outcomes.
The investigators will therefore evaluate the efficacy of CACICOL20® in a randomized, double-blinded clinical study, to evaluate its ability to promote corneal nerve regeneration, epithelial wound healing, and ocular surface recovery postoperatively.
Upon inclusion and signing of informed consent, patients undergo preoperative examination. Upon satisfying study criteria, patients are randomized to either treatment or placebo group. Group identity is masked to subjects and to investigators (double-blind). Subjects then undergo therapeutic laser treatment of the cornea in a single clinic, followed by instillation of treatment or placebo in the form of 3 eye drops total (to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery).
Postoperative eye examinations are conducted on days 2 and 7 and at month 6 and 12. Examinations include clinical measurement of various eye and corneal wound healing parameters.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cacicol20 | Experimental | Instillation of Cacicol20 eye drops after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery. |
|
| Placebo | Placebo Comparator | Instillation of placebo eye drops (vehicle missing the active ingredient) after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cacicol20 | Device | Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage recovery in subbasal nerve density. | Degree of corneal subbasal nerve regeneration at one year postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy. | 12 months postoperative |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage recovery in subbasal nerve density. | Degree of corneal subbasal nerve regeneration at 6 months postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy. | 6 months postoperative |
| Percentage of epithelial wound closure. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with adverse events as a measure of safety and tolerability. | Defined as reactions or complications beyond those normally expected after laser corneal surgery. Assessed by the investigator. | From operation day until 12 months postoperative. |
| Number of patients using supplementary eye treatments. |
Inclusion Criteria:
Exclusion Criteria:
Specific exclusion criteria for women
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| Name | Affiliation | Role |
|---|---|---|
| Sven Jarkman, MD PhD | Region Östergötland | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Linköping University Hospital | Linköping | SE-58183 | Sweden | |||
| Sahlgrenska University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11920675 | Background | Meddahi A, Alexakis C, Papy D, Caruelle JP, Barritault D. Heparin-like polymer improved healing of gastric and colic ulceration. J Biomed Mater Res. 2002 Jun 5;60(3):497-501. doi: 10.1002/jbm.1293. | |
| 18641578 | Background | Chebbi CK, Kichenin K, Amar N, Nourry H, Warnet JM, Barritault D, Baudouin C. [Pilot study of a new matrix therapy agent (RGTA OTR4120) in treatment-resistant corneal ulcers and corneal dystrophy]. J Fr Ophtalmol. 2008 May;31(5):465-71. doi: 10.1016/s0181-5512(08)72462-8. French. |
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| ID | Term |
|---|---|
| C535477 | Corneal dystrophy, epithelial basement membrane |
| C565155 | Epithelial Recurrent Erosion Dystrophy |
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| INDUSTRY |
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| Placebo | Device | Vehicle only in identical packaging, with identical dosage and administration route. |
|
A drop of sodium fluorescein liquid is applied to the cornea, and a digital photograph is taken at high magnification with a clinical slit lamp biomicroscope, using a blue illumination lamp. Area of open wound is measured from photographs and expressed as a percentage of the total treated area. |
| 2 and 7 days postoperative. |
| Postoperative pain score on the Visual Analog Scale. | Patient self-assessment using the subjective VAS scale (100 point scale). | Postoperative day 2, 7, month 6, 12 |
| Corneal haze level. | Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale. | Postoperative month 6, 12 |
| Number of postoperative recurrences of erosions. | As reported by the patient. | Postoperative month 12. |
| Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry. | Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry. | Postoperative month 6, 12 |
| Tear production level | Tear production level (in mm) measured by the Schirmer test without anesthetic. | Postoperative day 7, month 6, 12 |
| Tear quality | Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking. | Postoperative day 7, month 6, 12 |
| Improvement in visual acuity | Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level. | Postoperative day 7, month 6, 12 |
| Sub basal nerve density measured by clinical in vivo confocal microscopy | Sub basal nerve density level measured by clinical in vivo confocal microscopy. | Postoperative 6 and 12 months |
| Epithelial cell density measured by clinical in vivo confocal microscopy | Epithelial wing cell density measured by clinical in vivo confocal microscopy. | Postoperative 12 months |
Use of any supplementary eye treatments. |
| Operation day until 12 months postoperative. |
| Mölndal |
| Sweden |
| 19407024 | Background | Lagali N, Germundsson J, Fagerholm P. The role of Bowman's layer in corneal regeneration after phototherapeutic keratectomy: a prospective study using in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4192-8. doi: 10.1167/iovs.09-3781. Epub 2009 Apr 30. |
| 24569577 | Background | Germundsson J, Lagali N. Pathologically reduced subbasal nerve density in epithelial basement membrane dystrophy is unaltered by phototherapeutic keratectomy treatment. Invest Ophthalmol Vis Sci. 2014 Mar 25;55(3):1835-41. doi: 10.1167/iovs.13-12533. |
| 24105332 | Background | Cejkova J, Olmiere C, Cejka C, Trosan P, Holan V. The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage. Histol Histopathol. 2014 Apr;29(4):457-78. doi: 10.14670/HH-29.10.457. Epub 2013 Oct 9. |
| 22015067 | Background | De Monchy I, Labbe A, Pogorzalek N, Gendron G, M'Garrech M, Kaswin G, Labetoulle M. [Management of herpes zoster neurotrophic ulcer using a new matrix therapy agent (RGTA): A case report]. J Fr Ophtalmol. 2012 Mar;35(3):187.e1-6. doi: 10.1016/j.jfo.2011.09.002. Epub 2011 Oct 19. French. |
| 24937169 | Background | Kymionis GD, Liakopoulos DA, Grentzelos MA, Diakonis VF, Klados NE, Tsoulnaras KI, Tsilimbaris MK, Pallikaris IG. Combined topical application of a regenerative agent with a bandage contact lens for the treatment of persistent epithelial defects. Cornea. 2014 Aug;33(8):868-72. doi: 10.1097/ICO.0000000000000169. |