EPICAT: Effectiveness of Periocular Drug Injection in CATaract Surgery

Sponsor
Luigi Rondas (Other)
Overall Status
Recruiting
CT.gov ID
NCT05158699
Collaborator
European Society of Cataract and Refractive Surgeons (Other)
808
Enrollment
10
Locations
4
Arms
29.6
Anticipated Duration (Months)
80.8
Patients Per Site
2.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cystoid macular edema (CME) is a major cause of suboptimal postoperative visual acuity after cataract surgery. Topical steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs) are used to prevent CME. However, noncompliance with eye drops may compromise the effectiveness of treatment. Dropless periocular drug delivery during cataract surgery may improve the outcomes and cost-effectiveness of cataract surgery, and may alleviate the burden on homecare organizations.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

In a recent European multicentre study (PREvention of Macular EDema after cataract surgery; PREMED), it was demonstrated that the combination of topical corticosteroids and NSAIDs results in the lowest risk of developing CME after cataract surgery. However, noncompliance with eye drops may compromise the effectiveness of treatment. Noncompliance is often unintentional and related to forgetfulness or incorrect instillation, particularly in the elderly cataract surgery population.

The objective of this study is to evaluate the effectiveness of different treatments to prevent CME after cataract surgery, using either topical drugs (control group) or intra-/periocular injections (intervention groups).

The hypothesis of this study is that intra-/periocular anti-inflammatory drug delivery during cataract surgery is effective in preventing CME, with better health-related quality of life and improved cost-effectiveness compared to standard topical drug delivery.

The primary outcome measure is the change in central subfield mean macular thickness (CSMT) at 6 weeks postoperatively as compared to baseline. Secondary outcome measures are the incidence of CME; the incidence of clinically significant macular edema (CSME); mean corrected distance visual acuity (CDVA); para- and perifoveal thickness and total macular volume (TMV); intraocular pressure (IOP); anterior chamber inflammation; vision-related quality of life; and cost-effectiveness.

The design of this study is a European randomised controlled multicenter trial. The study population will consist of 808 patients aged 21 years or older who require cataract surgery in at least one eye. Patients with a foreseen increased risk of developing CME or ophthalmic disorders other than cataract will be excluded. Follow-up duration is 12 weeks. The study will be conducted over a period of 36 months.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
808 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A block randomization procedure will be followed to acquire equal number of subjects in every treatment group. Patients are randomly allocated to 1 of 4 treatment groups in a 1:1:1:1 ratio. The various study centres will be taken into account during randomization.A block randomization procedure will be followed to acquire equal number of subjects in every treatment group. Patients are randomly allocated to 1 of 4 treatment groups in a 1:1:1:1 ratio. The various study centres will be taken into account during randomization.
Masking:
Double (Care Provider, Outcomes Assessor)
Masking Description:
Masking will be achieved as much as possible. As there is an objective primary outcome, it will not be necessary to replace medicines by sham injections or placebo eye drops. Moreover, the ophthalmologist who performs the cataract surgery will not be blinded for treatment allocation of the subject. The study statistician, the data safety monitoring group, optometrists who perform the examinations (especially visual acuity) and observers who evaluate the examinations and OCTs will be masked when possible for treatment allocation.
Primary Purpose:
Prevention
Official Title:
The ESCRS EPICAT Study: Effectiveness of Periocular Drug Injection in CATaract Surgery
Actual Study Start Date :
Oct 13, 2021
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Apr 1, 2024

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: topical bromfenac & dexamethasone

bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperatively & dexamethasone 0.1% eye drops four times daily starting two days before surgery and continuing four times daily during the first postoperative week and one drop less per day every following week.

Drug: Bromfenac
Bromfenac topical eye drops (Yellox)
Other Names:
  • Yellox
  • Product code: EU/1/11/692
  • Drug: Dexamethasone
    Dexamethasone topical eye drops
    Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
  • Active Comparator: subconjunctival triamcinolone acetonide

    one subconjunctival injection of 10 mg triamcinolone acetonide during cataract surgery (TA, Triesence/Vistrec) in the inferotemporal quadrant, 6mm from the limbus.

    Drug: Triamcinolone Acetonide
    0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally
    Other Names:
  • Triesence or Vistrec
  • Product code (NL): RVG 106092
  • Active Comparator: intracameral ketorolac

    intracameral injection of ketorolac tromethamine solution during cataract surgery (Omidria). A 4ml vial of Omidria (ketorolac concentration 2.88mg/ml) is added to 500ml of the irrigation solution used during cataract surgery, resulting in a ketorolac concentration of 0.023mg/ml. At the end of the surgery, the anterior chamber will be filled with the ketorolac solution.

    Drug: Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular Solution
    Omidria is added to the irrigation fluid used during cataract surgery. At the end of surgery, the anterior chamber will be filled with the ketorolac solution.
    Other Names:
  • Omidria
  • Active Comparator: subconjunctival triamcinolone acetonide & intracameral ketorolac

    one subconjunctival injection of 10 mg triamcinolone acetonide & intracameral injection of ketorolac tromethamine solution (Omidria; 0.023mg/mL) during cataract surgery.

    Drug: Triamcinolone Acetonide
    0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally
    Other Names:
  • Triesence or Vistrec
  • Product code (NL): RVG 106092
  • Drug: Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular Solution
    Omidria is added to the irrigation fluid used during cataract surgery. At the end of surgery, the anterior chamber will be filled with the ketorolac solution.
    Other Names:
  • Omidria
  • Outcome Measures

    Primary Outcome Measures

    1. Change in central subfield mean macular thickness as a measurement of efficacy [Baseline, 6 weeks postoperatively]

      The primary endpoint is the change in central subfield mean macular thickness in the 1 mm area (central subfield macular thickness, CSMT) as compared to baseline within the first 6 weeks postoperatively, measured using Optical Coherence Tomography (OCT)

    Secondary Outcome Measures

    1. Change in central subfield mean macular thickness as a measurement of efficacy [Baseline, 12 weeks postoperatively]

      Measured using OCT

    2. No. of subjects developing clinically significant macular edema as a measurement of efficacy [Until 12 weeks postoperatively]

      The occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively

    3. Change in parafoveal retinal thickness in the central inner circle (1.0 - 3.0mm) as a measurement of efficacy [Baseline, 6 weeks and 12 weeks postoperatively]

      Measured using OCT

    4. Change in perifoveal retinal thickness in the central outer circle (3.0 - 6.0mm) as a measurement of efficacy [Baseline, 6 weeks and 12 weeks postoperatively]

      Measured using OCT

    5. Change in macular volume in the central 6.0mm area as a measurement of efficacy [Baseline, 6 weeks and 12 weeks postoperatively]

      Measured using OCT

    6. Change in corrected distance visual acuity (CDVA) as a measurement of efficacy [Baseline, 1 week, 6 weeks, and 12 weeks postoperatively]

      CDVA measurements will be taken using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts (logMAR)

    7. Change in Intraocular pressure (IOP) as a measurement of safety [Baseline, 1 week, 6 weeks, and 12 weeks postoperatively]

      IOP (in mmHg) will be measured by Goldmann applanation tonometry (preferred), Non-Contact Tonometry, or iCare tonometry

    8. Anterior chamber inflammation as a measurement of safety [Baseline, 1 week , 6 weeks, and 12 weeks postoperatively]

      using the Standardization of Uveitis Nomenclature (SUN) classification

    9. No. of subjects with Adverse Events as a measurement of safety and tolerability [Until 12 weeks postoperatively]

      An adverse event (AE) is defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the investigational product. All adverse events reported spontaneously by the subject or observed by the principal investigator or his staff will be recorded. Most frequently reported adverse events which might occur while using the study medication: abnormal sensation in the eye, pain or irritation, redness or headache while using eye drops; increased IOP and masking of infections while using corticosteroids; abnormal sensation in the eye, pain or irritation, conjunctival hyperaemia, inflammation and corneal edema after intracameral injection with phenylephrine/ketorolac.

    10. Patient reported outcome measures (PROMs): NEI VFQ-25 [Baseline and 12 weeks postoperatively]

      Patient satisfaction and vision-specific quality of life as measured by National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

    11. Patient reported outcome measures (PROMs): Catquest [Baseline and 12 weeks postoperatively]

      Patient satisfaction and vision-specific quality of life as measured by Catquest questionnaire.

    12. Patient reported outcome measures (PROMs): HUI3 [Baseline and 12 weeks postoperatively]

      Health-related quality of life as measured by HUI3 (Health Utility Index Mark 3) questionnaire.

    13. Patient reported outcome measures (PROMs): EQ-5D-5L [Baseline and 12 weeks postoperatively]

      Health-related quality of life as measured by EQ-5D-5L questionnaire.

    14. Quality Adjusted Life Years (QALYs) [Baseline until 12 weeks postoperatively]

      Calculated based on generic health-related quality of life, using the EQ-5D-5L and HUI-3 questionnaires

    15. Costs per patient [Baseline until 12 weeks postoperatively]

      Cost per patient, including valuation of resource use by using the Dutch guidelines for cost-analyses or cost prices provided by the medical center.

    16. Incremental cost-effectiveness ratios (ICERs): QALY [Baseline until 12 weeks postoperatively]

      Evaluation of cost-effectiveness by using calculated costs per quality-adjusted life years (QALYs)

    17. Incremental cost-effectiveness ratios (ICERs): NEI VFQ-25 [Baseline until 12 weeks postoperatively]

      Calculated costs per clinically improved patient on the NEI VFQ-25 questionnaire

    18. Incremental cost-effectiveness ratios (ICERs): Catquest [Baseline until 12 weeks postoperatively]

      Calculated costs per clinically improved patient on the Catquest questionnaire

    19. Incremental cost-effectiveness ratios (ICERs): Visual acuity [Baseline until 12 weeks postoperatively]

      Calculated costs per patient with clinical improvement in (un)corrected distance visual acuity

    20. Budget impact [Baseline until 12 weeks postoperatively]

      Reported as a difference in costs. Different scenario's will be compared to investigate the impact of various levels of implementation (e.g. 25%, 50%, 75% of eligible patients).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • who are undergoing routine phacoemulsification (one eye per patient);

    • who are 21 years or older;

    • who should be able to communicate properly and understand instructions.

    • willing and/or able to comply with the scheduled visits and other study procedures.

    Exclusion Criteria:
    • patients who already participated with their contralateral eye;

    • combined surgery (e.g. combined phacoemulsification and trabeculectomy);

    • patients with an increased risk of developing cystoid macular edema (CME) in the study eye (e.g. diabetes mellitus, previous retinal venous occlusion, or a history of uveitis, macular edema, epiretinal membrane, or previous retinal surgery);

    • patients who developed CME after cataract surgery in the contralateral eye;

    • patients with cystoid macular changes in the study eye at baseline;

    • patients with an increased risk of developing perioperative complications (e.g. Fuchs' endothelial dystrophy);

    • patients with permanent moderate visual impairment in the contralateral eye (decimal visual acuity less than 0.3);

    • patients with a history of steroid induced IOP rise or glaucomatous visual field loss;

    • patients using drugs that reduce or increase the risk of macular edema (e.g., periocular or intraocular corticosteroid, NSAID, or antivascular endothelial growth factor (VEGF) injection; topical corticosteroid or NSAID use; systemic corticosteroids (>= 20mg prednisolon), methotrexate, biologicals, or acetazolamide), or in the previous 4 months;

    • patients with a contraindication for any of the investigated drugs;

    • patients who are cardiovascular unstable;

    • patients who have a history of hyperthyroidism.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Hospital of the Brothers of Saint John of GodViennaAustria1020
    2Vienna Institute for Research in Ocular Surgery, Hanusch KrankenhausViennaAustriaA-1140
    3Goethe UniversityFrankfurt am MainGermany60590
    4Deventer ZiekenhuisDeventerNetherlands7416SE
    5Zuyderland Medisch CentrumHeerlenNetherlands6419 PC
    6University Eye Clinic Maastricht UMC+MaastrichtNetherlands6229HX
    7Canisius Wilhelmina Ziekenhuis NijmegenNijmegenNetherlands6532SZ
    8Elisabeth-Twee Steden Ziekenhuis, locatie ElisabethTilburgNetherlands5022GC
    9Gelre ZiekenhuizenZutphenNetherlands7207AE
    10University Hospital CoimbraCoimbraPortugal3000-075

    Sponsors and Collaborators

    • Luigi Rondas
    • European Society of Cataract and Refractive Surgeons

    Investigators

    • Principal Investigator: Nienke Visser, Dr., Universiteitskliniek voor Oogheelkunde Maastricht UMC+

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Luigi Rondas, Master of Science, PhD student, Academisch Ziekenhuis Maastricht
    ClinicalTrials.gov Identifier:
    NCT05158699
    Other Study ID Numbers:
    • NL72427.068.19
    • 2019-004890-21
    First Posted:
    Dec 15, 2021
    Last Update Posted:
    Dec 15, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Luigi Rondas, Master of Science, PhD student, Academisch Ziekenhuis Maastricht
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 15, 2021