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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-004890-21 | EudraCT Number |
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Results of interim analysis: stop the trial due to one group being significantly different from the other three groups. Furthermore, shortage of study medication.
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| Name | Class |
|---|---|
| European Society of Cataract and Refractive Surgeons | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| topical bromfenac & dexamethasone | Active Comparator | 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. |
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| subconjunctival triamcinolone acetonide | Active Comparator | one subconjunctival injection of 10 mg triamcinolone acetonide during cataract surgery (TA, Triesence/Vistrec) in the inferotemporal quadrant, 6mm from the limbus. |
|
| intracameral ketorolac | Active Comparator | 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. |
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| subconjunctival triamcinolone acetonide & intracameral ketorolac | Active Comparator | one subconjunctival injection of 10 mg triamcinolone acetonide & intracameral injection of ketorolac tromethamine solution (Omidria; 0.023mg/mL) during cataract surgery. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bromfenac | Drug | Bromfenac topical eye drops (Yellox) |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in central subfield mean macular thickness as a measurement of efficacy | Measured using OCT | Baseline, 12 weeks postoperatively |
| No. of subjects developing clinically significant macular edema as a measurement of efficacy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nienke Visser, Dr. | Universiteitskliniek voor Oogheelkunde Maastricht UMC+ | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of the Brothers of Saint John of God | Vienna | 1020 | Austria | |||
| Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus |
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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.
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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.
| Dexamethasone | Drug | Dexamethasone topical eye drops |
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| Triamcinolone Acetonide | Drug | 0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally |
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| Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular Solution | Drug | 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. |
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The occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively
| Until 12 weeks postoperatively |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Anterior chamber inflammation as a measurement of safety | Grading will be performed using the classification of the "Standardization of Uveitis Nomenclature" (SUN) working group using a 2mm long and 1mm wide slit beam:
| Baseline, 1 week , 6 weeks, and 12 weeks postoperatively |
| 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 |
| 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). From 25 questions, the original numeric values given (1-10) are converted to a 0 to 100 scale, so that the scores are set between 0 points (worst outcome) and 100 points (best outcome). | Baseline and 12 weeks postoperatively |
| Patient reported outcome measures (PROMs): Catquest-9SF | Patient satisfaction and vision-specific quality of life as measured by the Catquest-9SF questionnaire. The possible range in Catquest scores are -3.94 (no difficulties) to +3.52 (great difficulties). | Baseline and 12 weeks postoperatively |
| Patient reported outcome measures (PROMs): HUI3 | Health-related quality of life as measured by HUI3 (Health Utility Index Mark 3) questionnaire. The HUI3 questionnaire consists of 8 attributes, including vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. For each attribute, the HUI3 questionnaire provides utility (preference) scores on a generic scale where dead = 0.00 and perfect health = 1.00. | Baseline and 12 weeks postoperatively |
| Patient reported outcome measures (PROMs): EQ-5D-5L | Health-related quality of life as measured by the 5-level EQ-5D version (EQ-5D-5L) questionnaire. The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).
| Baseline and 12 weeks postoperatively |
| 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 |
| 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 |
| 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 |
| 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 |
| Incremental cost-effectiveness ratios (ICERs): Catquest | Calculated costs per clinically improved patient on the Catquest questionnaire | Baseline until 12 weeks postoperatively |
| 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 |
| 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 |
| Vienna |
| A-1140 |
| Austria |
| Goethe University | Frankfurt am Main | 60590 | Germany |
| Amphia | Breda | 4818 CK | Netherlands |
| Deventer Ziekenhuis | Deventer | 7416SE | Netherlands |
| Zuyderland Medisch Centrum | Heerlen | 6419 PC | Netherlands |
| University Eye Clinic Maastricht UMC+ | Maastricht | 6229HX | Netherlands |
| Canisius Wilhelmina Ziekenhuis Nijmegen | Nijmegen | 6532SZ | Netherlands |
| Elisabeth-Twee Steden Ziekenhuis, locatie Elisabeth | Tilburg | 5022GC | Netherlands |
| University Hospital Coimbra | Coimbra | 3000-075 | Portugal |
| ID | Term |
|---|---|
| D008269 | Macular Edema |
| D012164 | Retinal Diseases |
| D002386 | Cataract |
| D007905 | Lens Diseases |
| D005128 | Eye Diseases |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D012162 | Retinal Degeneration |
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| ID | Term |
|---|---|
| C053083 | bromfenac |
| D003907 | Dexamethasone |
| D014222 | Triamcinolone Acetonide |
| D014221 | Triamcinolone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
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