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Keratoconus, UnstablePhase 4NCT04168112

Intracanalicular Dexamethasone Insert for Post-Corneal Cross-Linking Inflammation and Pain- The LINK Study

A Phase 4 study testing Dextenza and Prednisolone Acetate in people with Keratoconus, Unstable and Collagen Crosslinking, run by Sight Medical Doctors PLLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

There is no standard of care medication regimen for the management of pain and inflammation post-corneal crosslinking (CXL), although most cornea specialists agree on use of an antibiotic and steroid eye drop in the immediate postoperative period. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dextenza and Prednisolone Acetate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
12 Feb 2020to 5 Apr 2023
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Progressive keratoconus with planned corneal cross-linking in one or both eyes
  • Age 18 years and older
  • Ability to provide informed consent for procedures
  • Ability to attend scheduled follow up visits

Who cannot join

  • Age less than 18
  • Pregnancy/currently breast-feeding
  • Inability to provide informed consent
  • Documented adverse reaction to steroid (e.g. "steroid responder", allergy, etc)
  • Punctal stenosis
  • Previous corneal transplant surgery
Show all 12Show fewer
  • Systemic concomitant use of controlled substance for pain management (i.e. oxycodone)
  • Concurrent use of topical steroid eye drops
  • Systemic, topical or intravitreal steroid use within 1 month of baseline
  • Active history of chronic or recurrent inflammatory eye disease in either eye
  • History of ocular herpetic infection (inclusive of Herpes Simplex 1/2, Varicella Zoster, Epstein Barr, Cytomegalovirus)
  • History of neurotrophic keratitis, uncontrolled diabetes, or other disease entities that may preclude proper healing

Trial locations and contacts

1 site in 1 country.

United States1 site
  • SightMD

    Babylon, New York, 11702

Other trials in United States

About this study

There is no standard of care medication regimen for the management of pain and inflammation post-corneal crosslinking (CXL), although most cornea specialists agree on use of an antibiotic and steroid eye drop in the immediate postoperative period. However, steroid tapering schedule and use of additional topical non-steroidal anti-inflammatory (NSAID) eyedrops vary amongst practitioners. The goal of this study is to compare postoperative pain scores between patients receiving a tapering dose of topical steroids over 1-month post-CXL, versus those receiving an intracanalicular dexamethasone insert.

Read the detailed description

Keratoconus is a progressive ectatic disease of the cornea, leading to worsening of astigmatism and vision over time. With FDA approval of corneal collagen cross-linking (CXL), we now have the ability to halt the progression of keratoconus and prevent further vision loss in these patients. Although CXL has now become standard of care, the immediate post-operative period can be quite painful despite use of anti-inflammatory medications/eye drops. The goal of this study is to evaluate the efficacy of an intracanalicular dexamethasone insert in reduction of post-CXL pain as compared to routine steroid eye drop therapy.

To date, no studies have been performed evaluating the success of an intracanalicular dexamethasone insert for the treatment of postoperative inflammation and pain in corneal cross-linking patients. Oftentimes, patients experience a great deal of discomfort post-CXL, which may also make it difficult to apply eye drops in the correct fashion. Use of a dexamethasone insert alleviates the need for postoperative steroid eye drops and may provide increased pain relief post-CXL as compared to topical therapy. This will be a head-to-head study where steroid therapy (topical or insert) will begin in a standard fashion on the date of CXL. This will allow for accurate comparison of a 4-week taper of topical steroids, versus a dexamethasone insert designed to release steroid for 30 days.

Being tested
Dextenza, Prednisolone Acetate
Keywords
Collagen Crosslinking, Keratoconus, Dexamethasone, Intracanalicular Insert
Medical subject headings
Keratoconus, Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DextenzaDrug

    Also called Intracanalicular dexamethasone insert

    Placement of intracanalicular dexamethasone insert for post-crosslinking inflammation and pain

  • Prednisolone AcetateDrug

    post-crosslinking eye drop prednisolone acetate given in a tapering schedule over 1 month

Study groups in NCT04168112
Study groupRoleWhat they receive
Group AExperimentalIntracanalicular dexamethasone insert is placed on day of crosslinking (CXL); patients will still receive postoperative fluoroquinolone (or other class in case of allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye QID x 10 days).
Receives: Drug: Dextenza
Group BActive comparatorPatients are placed on standard postoperative regimen of postoperative fluoroquinolone (or other class in case of allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye QID x 10 days) and Prednisolone acetate 1% ophthalmic solution tapered over 1 month in the following schedule: QID x1 week, TID x 1 week, BID x 1 week, and Qday x 1 week.
Receives: Drug: Prednisolone Acetate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Degree of Postoperative Pain Between Groups From Date of Surgery Through 1 Month Post-CXL (Day of Surgery, Postoperative Days 1 ,3, 7, Postoperative Weeks 2 ,3 and 4)

    Utilizing the standardized Wong-Baker visual analog pain scale, graded from 0 to 10 (no pain to increasingly worse pain (worst at 10/10))

    Measured: Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)

  2. Degree and Improvement of Ocular Surface Inflammation Between Groups From Date of Surgery Through 1 Month Post-CXL (Day of Surgery, Postoperative Days 1 ,3, 7, Postoperative Weeks 2 ,3 and 4)

    Assessment of corneal edema/cells (if any), degree of conjunctiva injection (if any) Grading will be from 0 to 4, with "0" being no conjunctival injection, and "4" indicating severe, diffuse conjunctival injection. Presence of corneal cells will be noted if present or absent.

    Measured: assessed at day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)

Secondary outcomes (3)
  1. Rate of Corneal Re-epithelialization

    Evaluation of rate of corneal re-epithelialization post-crosslinking at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4

    Measured: Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)

  2. Subjective 'Ease of Postoperative Care' for Patients Receiving Standard Topical Steroid Eye Drop Taper vs. Dexamethasone Insert

    Questionnaire at final visit regarding ease of postoperative eye drop use

    Measured: postoperative week 4 (POW4)

  3. Notation of Need for Use of "Rescue" Pain Medication

    Use of oral non-steroidal anti-inflammatory (NSAID), acetaminophen, prescribed pain medication) between groups

    Measured: Assessement of use of additional/adjunctive pain/antiinflammatory medications will be done for each patient at postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2019
  2. Study start12 Feb 2020
  3. Primary completion24 Oct 2022
  4. Study completion5 Apr 2023

Resources

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
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Model description
Two cohorts of patients will be studied (10 patients each group). Cohort A: intracanalicular dexamethasone insert is placed on day of crosslinking (CXL); patients will still receive postoperative fluoroquinolone (or another class if allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye 4 times daily x 10 days). Cohort B: Patients are placed on standard postoperative regimen of postoperative fluoroquinolone antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye 4 times daily (QID) x 10 days) and Prednisolone acetate 1% ophthalmic solution tapered over 1 month in the following schedule: 4 times daily x1 week, three times daily (TID) x 1 week, twice daily (BID) x 1 week, and once daily (QD) x 1 week).
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04168112
Sponsor's protocol ID
LINK1
Status last verified
Jan 2024
First submitted
13 Nov 2019
Last updated
30 Jan 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: We do not plan to share individual participant data (IPD) with other researchers. However, any adverse events will be reported to the governing institutional review board (IRB) and Ocular Therapeutix and FDA if applicable.

Publications

  • Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb;42(4):297-319. doi: 10.1016/s0039-6257(97)00119-7.

    PubMed 9493273
  • Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984 Jan-Feb;28(4):293-322. doi: 10.1016/0039-6257(84)90094-8.

    PubMed 6230745
  • Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.

    PubMed 12719068
  • Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006 Feb;32(2):279-83. doi: 10.1016/j.jcrs.2005.12.092.

    PubMed 16565005
  • Hoyer A, Raiskup-Wolf F, Sporl E, Pillunat LE. [Collagen cross-linking with riboflavin and UVA light in keratoconus. Results from Dresden]. Ophthalmologe. 2009 Feb;106(2):133-40. doi: 10.1007/s00347-008-1783-2. German.

    PubMed 18604541
  • Wollensak G, Sporl E, Seiler T. [Treatment of keratoconus by collagen cross linking]. Ophthalmologe. 2003 Jan;100(1):44-9. doi: 10.1007/s00347-002-0700-3. German.

    PubMed 12557025
  • Snibson GR. Collagen cross-linking: a new treatment paradigm in corneal disease - a review. Clin Exp Ophthalmol. 2010 Mar;38(2):141-53. doi: 10.1111/j.1442-9071.2010.02228.x.

    PubMed 20398104
  • Peyman A, Kamali A, Khushabi M, Nasrollahi K, Kargar N, Taghaodi M, Razmjoo H, Fazel F, Salesi A. Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial. Adv Biomed Res. 2015 Nov 23;4:245. doi: 10.4103/2277-9175.170240. eCollection 2015.

    PubMed 26693470
  • Ghanem VC, Ghanem RC, de Oliveira R. Postoperative pain after corneal collagen cross-linking. Cornea. 2013 Jan;32(1):20-4. doi: 10.1097/ICO.0b013e31824d6fe3.

    PubMed 22547128
  • Zarei-Ghanavati S, Jafarpour S, Radyn-Majd A, Hosseinikhah-Manshadi H. Evaluation of early postoperative ocular pain after photorefractive keratectomy and corneal crosslinking. J Cataract Refract Surg. 2018 May;44(5):566-570. doi: 10.1016/j.jcrs.2018.02.019. Epub 2018 May 9.

    PubMed 29753555
  • Serna-Ojeda JC, Santana-Cruz O, Quiroz-Casian N, Gonzalez-Mendoza E, Mercado-Orozco JL, Navas A, Lichtinger A, Graue-Hernandez EO. Pain Management in Corneal Collagen Crosslinking for Keratoconus: A Comparative Case Series. J Ocul Pharmacol Ther. 2019 Jul/Aug;35(6):325-330. doi: 10.1089/jop.2019.0021. Epub 2019 Jun 19.

    PubMed 31216215
  • Kocluk Y, Cetinkaya S, Sukgen EA, Gunay M, Mete A. Comparing the effects of two different contact lenses on corneal re-epithelialization after corneal collagen cross-linking. Pak J Med Sci. 2017 May-Jun;33(3):680-685. doi: 10.12669/pjms.333.12241.

    PubMed 28811794
  • Nattis AS, Rosenberg ED, Rasool F. Intracanalicular dexamethasone insert for post-corneal crosslinking inflammation and pain: the LINK study. J Cataract Refract Surg. 2023 Nov 1;49(11):1114-1119. doi: 10.1097/j.jcrs.0000000000001279.

    PubMed 37532250

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dextenza and Prednisolone Acetate in people with Keratoconus, Unstable and Collagen Crosslinking, run by Sight Medical Doctors PLLC at 1 site in United States.

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 4 inclusion and 12 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 30 Jan 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 United States. 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?

Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 in Degree of Postoperative Pain Between Groups From Date of Surgery Through 1 Month Post-CXL (Day of Surgery, Postoperative Days 1 ,3, 7, Postoperative Weeks 2 ,3 and 4) (time frame: Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)). 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 NCT04168112, which also lists 13 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 30 Jan 2024.

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