Effectiveness of Periocular Drug Injection in CATaract Surgery

Cataract Clinical Trial

— EPICAT  

Official title:

The ESCRS EPICAT Study: Effectiveness of Periocular Drug Injection in CATaract Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05158699
• Other study ID #: NL72427.068.19
• Secondary ID: 2019-004890-21
• Status: Recruiting
• Phase: Phase 3
• Start date: October 13, 2021
• Est. completion date: April 1, 2024

Study information

• Verified date: December 2021
• Source: Academisch Ziekenhuis Maastricht
• Contact: Luigi UE Rondas, Drs.
• Phone: +31 (0)43 387 1779
• Email: luigi.rondas[@]mumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 808
• Est. completion date: April 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cataract
• Cystoid Macular Edema
• Edema
• Eye Diseases
• Lens Diseases
• Macular Edema
• Retinal Disease
• Retinal Diseases

Intervention

Drug:
• Bromfenac
Bromfenac topical eye drops (Yellox)
• Dexamethasone
Dexamethasone topical eye drops
• Triamcinolone Acetonide
0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally
• 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.

Locations

Country	Name	City	State
Austria	Hospital of the Brothers of Saint John of God	Vienna
Austria	Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus	Vienna
Germany	Goethe University	Frankfurt am Main
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	University Eye Clinic Maastricht UMC+	Maastricht
Netherlands	Canisius Wilhelmina Ziekenhuis Nijmegen	Nijmegen
Netherlands	Elisabeth-Twee Steden Ziekenhuis, locatie Elisabeth	Tilburg
Netherlands	Gelre Ziekenhuizen	Zutphen
Portugal	University Hospital Coimbra	Coimbra

Sponsors (2)

Lead Sponsor	Collaborator
Luigi Rondas	European Society of Cataract and Refractive Surgeons

Countries where clinical trial is conducted

Austria,  Germany,  Netherlands,  Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in central subfield mean macular thickness as a measurement of efficacy	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)	Baseline, 6 weeks postoperatively
Secondary	Change in central subfield mean macular thickness as a measurement of efficacy	Measured using OCT	Baseline, 12 weeks postoperatively
Secondary	No. of subjects developing clinically significant macular edema as a measurement of efficacy	The occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively	Until 12 weeks postoperatively
Secondary	Change in parafoveal retinal thickness in the central inner circle (1.0 - 3.0mm) as a measurement of efficacy	Measured using OCT	Baseline, 6 weeks and 12 weeks postoperatively
Secondary	Change in perifoveal retinal thickness in the central outer circle (3.0 - 6.0mm) as a measurement of efficacy	Measured using OCT	Baseline, 6 weeks and 12 weeks postoperatively
Secondary	Change in macular volume in the central 6.0mm area as a measurement of efficacy	Measured using OCT	Baseline, 6 weeks and 12 weeks postoperatively
Secondary	Change in corrected distance visual acuity (CDVA) as a measurement of efficacy	CDVA measurements will be taken using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts (logMAR)	Baseline, 1 week, 6 weeks, and 12 weeks postoperatively
Secondary	Change in Intraocular pressure (IOP) as a measurement of safety	IOP (in mmHg) will be measured by Goldmann applanation tonometry (preferred), Non-Contact Tonometry, or iCare tonometry	Baseline, 1 week, 6 weeks, and 12 weeks postoperatively
Secondary	Anterior chamber inflammation as a measurement of safety	using the Standardization of Uveitis Nomenclature (SUN) classification	Baseline, 1 week , 6 weeks, and 12 weeks postoperatively
Secondary	No. of subjects with Adverse Events as a measurement of safety and tolerability	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.	Until 12 weeks postoperatively
Secondary	Patient reported outcome measures (PROMs): NEI VFQ-25	Patient satisfaction and vision-specific quality of life as measured by National Eye Institute Visual Function Questionnaire (NEI VFQ-25).	Baseline and 12 weeks postoperatively
Secondary	Patient reported outcome measures (PROMs): Catquest	Patient satisfaction and vision-specific quality of life as measured by Catquest questionnaire.	Baseline and 12 weeks postoperatively
Secondary	Patient reported outcome measures (PROMs): HUI3	Health-related quality of life as measured by HUI3 (Health Utility Index Mark 3) questionnaire.	Baseline and 12 weeks postoperatively
Secondary	Patient reported outcome measures (PROMs): EQ-5D-5L	Health-related quality of life as measured by EQ-5D-5L questionnaire.	Baseline and 12 weeks postoperatively
Secondary	Quality Adjusted Life Years (QALYs)	Calculated based on generic health-related quality of life, using the EQ-5D-5L and HUI-3 questionnaires	Baseline until 12 weeks postoperatively
Secondary	Costs per patient	Cost per patient, including valuation of resource use by using the Dutch guidelines for cost-analyses or cost prices provided by the medical center.	Baseline until 12 weeks postoperatively
Secondary	Incremental cost-effectiveness ratios (ICERs): QALY	Evaluation of cost-effectiveness by using calculated costs per quality-adjusted life years (QALYs)	Baseline until 12 weeks postoperatively
Secondary	Incremental cost-effectiveness ratios (ICERs): NEI VFQ-25	Calculated costs per clinically improved patient on the NEI VFQ-25 questionnaire	Baseline until 12 weeks postoperatively
Secondary	Incremental cost-effectiveness ratios (ICERs): Catquest	Calculated costs per clinically improved patient on the Catquest questionnaire	Baseline until 12 weeks postoperatively
Secondary	Incremental cost-effectiveness ratios (ICERs): Visual acuity	Calculated costs per patient with clinical improvement in (un)corrected distance visual acuity	Baseline until 12 weeks postoperatively
Secondary	Budget impact	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).	Baseline until 12 weeks postoperatively