PRevention of Macular EDema After Cataract Surgery (PREMED)
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Purpose
Cystoid macular edema (CME) is a swelling of the central and most important part of the retina. It is a common cause of vision loss after cataract surgery. In the last few years, several new treatments have been tried to address the problem of CME after cataract surgery in diabetic and non-diabetic patients. However, no randomised controlled clinical trial (RCT) has compared all the currently existing preventive interventions and no study has been conducted to investigate whether combining different preventive strategies has an additional effect. Therefore, the investigators will perform a large RCT with the aim to provide more definite evidence-based recommendations for clinical guidelines to prevent the occurrence of CME after cataract surgery in patients with and without diabetes mellitus (DM). The outcomes of this RCT will be of benefit to all cataract surgeons.
| Condition | Intervention | Phase |
|---|---|---|
|
Macular Edema Cataract Diabetes Mellitus |
Drug: Bromfenac Drug: Dexamethasone Drug: Bevacizumab Drug: Triamcinolone Acetonide |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention |
| Official Title: | PRevention of Macular EDema After Cataract Surgery |
- Change in central subfield mean macular thickness as a measurement of efficacy [ Time Frame: 6 weeks postoperatively ] [ Designated as safety issue: No ]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.
- No. of subjects developing clinically significant macular edema as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]The secondary endpoint is the occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively.
- Change in corrected distance visual acuity (CDVA) as a measurement of efficacy [ Time Frame: 6 postoperatively ] [ Designated as safety issue: No ]CDVA measurements will be taken using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts (logMAR).
- Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy [ Time Frame: 6 weeks postoperatively ] [ Designated as safety issue: No ]Measured using Optical Coherence Tomography (OCT)
- Intraocular pressure (IOP) as a measurement of safety [ Time Frame: 6 postoperatively ] [ Designated as safety issue: Yes ]IOP (in mmHg) will be measured by Goldmann applanation tonometry
- Health-related quality of life as a measurement of efficacy and tolerability [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Using the Health Utility Index mark 3 (HUI-3)
- No. of subjects with Adverse Events as a measurement of safety and tolerability [ Time Frame: 6 weeks postoperatively ] [ Designated as safety issue: Yes ]
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; retinal detachment, thrombo-embolic events, endophthalmitis and anterior chamber reactions after intravitreal injections of bevacizumab.
- Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy [ Time Frame: 6 weeks postoperatively ] [ Designated as safety issue: No ]Using OCT
- Change in macular volume as a measurement of efficacy [ Time Frame: 6 postoperatively ] [ Designated as safety issue: No ]Using OCT
- Vision-related quality of life as a measurement of efficacy and tolerability [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Using the National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ 25)
- Cost-effectiveness [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Incremental cost-effectiveness ratios of the costs per quality-adjusted life year (QALY) and costs per improved patient on the NEI VFQ-25 and HUI-3.
- Change in corrected distance visual acuity (CDVA) as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]CDVA measurements will be taken using ETDRS visual acuity testing charts (logMAR).
- Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Measured using Optical Coherence Tomography (OCT)
- Intraocular pressure (IOP) as a measurement of safety [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: Yes ]IOP (in mmHg) will be measured by Goldmann applanation tonometry
- No. of subjects with Adverse Events as a measurement of safety and tolerability [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: Yes ]
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; retinal detachment, thrombo-embolic events, endophthalmitis and anterior chamber reactions after intravitreal injections of bevacizumab.
- Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Using OCT
- Change in macular volume as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Using OCT
- Change in central subfield mean macular thickness as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ] [ Designated as safety issue: No ]Using OCT
| Estimated Enrollment: | 1350 |
| Study Start Date: | June 2013 |
| Estimated Study Completion Date: | June 2015 |
| Estimated Primary Completion Date: | March 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Non diabetics: bromfenac
bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperatively
|
Drug: Bromfenac
n/a
Other Names:
|
|
Active Comparator: Non diabetics: dexamethasone
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: Dexamethasone
n/a
Other Names:
|
|
Active Comparator: Non diabetics: bromfenac & dexamethasone
bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative & 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
n/a
Other Names:
Drug: Dexamethasone
n/a
Other Names:
|
|
Active Comparator: Diabetics: eye drops
bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative & 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
n/a
Other Names:
Drug: Dexamethasone
n/a
Other Names:
|
|
Active Comparator: Diabetics: eye drops & TA
bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative & 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 & a peroperative subconjunctival injection of 40 mg triamcinolone acetonide (TA, Triesence) |
Drug: Bromfenac
n/a
Other Names:
Drug: Dexamethasone
n/a
Other Names:
Drug: Triamcinolone Acetonide
n/a
Other Names:
|
|
Active Comparator: Diabetics: eye drops & bevacizumab
bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative & 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 & a peroperative intravitreal injection of 1.25 mg bevacizumab (Avastin) |
Drug: Bromfenac
n/a
Other Names:
Drug: Dexamethasone
n/a
Other Names:
Drug: Bevacizumab
n/a
Other Names:
|
|
Active Comparator: Diabetics: eye drops, TA & bevacizumab
bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative, 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 & a peroperative subconjunctival injection of 40 mg triamcinolone acetonide (TA) & a peroperative intravitreal injection of 1.25 mg bevacizumab |
Drug: Bromfenac
n/a
Other Names:
Drug: Dexamethasone
n/a
Other Names:
Drug: Bevacizumab
n/a
Other Names:
Drug: Triamcinolone Acetonide
n/a
Other Names:
|
Detailed Description:
The objective of this study is to evaluate the effect of different preventive strategies on the occurrence of macular edema after cataract surgery in non-diabetic and diabetic patients. The design of the study is a multicentre randomised controlled clinical trial with a duration of 33 months. The study population will consist of 1050 non-diabetic patients and 300 patients with diabetes mellitus (DM) who require cataract surgery in at least one eye. All patients will receive a phacoemulsification for cataract and placement of a posterior chamber intraocular lens (IOL).
In the non-diabetic population, the patients will receive either bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative, 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 or a combination of both drugs.
In the diabetic population patients will receive either:
- Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose;
- Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose and a subconjunctival injection of 40 mg triamcinolone acetonide (Triesence);
- Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose and an intravitreal injection of 1.25 mg bevacizumab (Avastin);
- Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose, a subconjunctival injection of 40 mg triamcinolone acetonide and an intravitreal injection of 1.25 mg bevacizumab.
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 postoperative.
The secondary endpoint is the occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively. Other study endpoints are mean CDVA in logMAR at 6 weeks and 12 weeks postoperatively; OCT measured average retinal thickness in the central inner circle (3mm), the outer circle (6mm), and the macular volume at 6 weeks and 12 weeks postoperatively; intraocular pressure at 6 weeks and 12 weeks postoperatively; health-related and vision-related quality of life at 12 weeks postoperatively; incremental cost-effectiveness ratios of the costs per quality-adjusted life year (QALY) and costs per improved patient on the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and Health Utility Index (HUI-3).
In case of clinically significant macular edema, treatment will be initiated and its effect will be part of the evaluation at 12 weeks. Medical data of all patients who develop macular edema during this study will be checked at least 6 months after surgery.
Eligibility| Ages Eligible for Study: | 21 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- All patients undergoing routine phacoemulsification (one eye per patient)
- willing and/or able to comply with the scheduled visits and other study procedures.
- able to communicate properly and understand instructions.
- accepting possible off-label use of intravitreal bevacizumab and/or subconjunctival preservative-free TA.
Exclusion Criteria:
- age below 21 years old;
- patients already participating in another clinical study;
- functional monoculus;
- previous ocular surgery;
diabetic patients with
- macular edema with a CSMT ≥450 µm;
- very severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) requiring panretinal photocoagulation or vitrectomy;
- vitreous haemorrhage present during preoperative visit(s);
- non-diabetic patients with cystoid macular edema (CME);
- history of glaucoma, use of anti-glaucomatous medication or steroid-induced IOP elevation that required IOP-lowering treatment;
- IOP ≥ 25 mmHg;
- post-traumatic cataract;
- history of any ocular inflammation or uveitis;
- history of pseudoexfoliation syndrome, which is expected to cause peroperative complications (e.g. transillumination defects at the pupillary margin or zonulolysis);
- history of Fuchs' endothelial dystrophy or cornea guttata 3+;
- history of retinal vein occlusion;
- any macular pathology that might influence VA, other than diabetic macular edema(e.g. macular pucker, macular hole, severe age-related macular degeneration (AMD))
- cerebrovascular accident, myocardial infarction or other thromboembolic events in the previous 3 months;
- history of recurrent thromboembolic events;
- history of severe systemic bleeding in the previous 3 months;
- major surgery in the previous 3 months;
- use of intravitreal bevacizumab or ranibizumab in the previous 6 weeks or intravitreal aflibercept in the previous 10 weeks;
- use of intra- or periocular corticosteroids injection in the previous 4 months;
- current use of topical non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids;
- use of systemic corticosteroids (≥ 20mg prednisolone or equivalence);
- history of relevant adverse events, including serious adverse events (SAE) occurring after administration of NSAIDs, acetylsalicylic acid, sodium sulphite, corticosteroids or bevacizumab;
- contraindications for use of topical NSAIDs, topical or subconjunctival corticosteroids or intravitreal bevacizumab or related drugs (e.g. tuberculosis, pregnancy, planning to become pregnant in the coming 6 months, nursing mothers);
- combined surgery (e.g. combined phacoemulsification and trabeculectomy or phacoemulsification and DSAEK)
Data of subjects without a baseline OCT of sufficient quality will be excluded from analysis. However, these patients cannot be excluded from the study, as they already received (part of) the study medication.
Contacts and Locations| Contact: Rudy MM Nuijts, MD, PhD | +31 43 387 7125 | rudy.nuijts@mumc.nl |
| Contact: Laura HP Wielders, MD | +31 43 387 7131 | laura.wielders@mumc.nl |
| Austria | |
| Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus | Not yet recruiting |
| Vienna, Austria, A-1140 | |
| Contact: prof. O. Findl, MD, PhD +43 67 6382 8538 oliver@findl.at | |
| Principal Investigator: prof. O. Findl, MD, PhD | |
| Belgium | |
| University Hospital Antwerp | Not yet recruiting |
| Edegem, Belgium, B-2650 | |
| Contact: prof. M. Tassignon, MD, PhD +32 3 821 33 77 marie-jose.tassignon@uza.be | |
| Principal Investigator: prof. M. Tassignon, MD, PhD | |
| Germany | |
| Augenklinik Spreebogen | Not yet recruiting |
| Berlin, Germany, 10559 | |
| Contact: prof. M. Tetz, MD, PhD +49 30 3980 98 0 manfred.tetz@atk-spreebogen.de | |
| Principal Investigator: prof. M. Tetz, MD, PhD | |
| Goethe University | Not yet recruiting |
| Frankfurt am Main, Germany, 60590 | |
| Contact: prof. T. Kohnen, MD, PhD +49 69 6301 3945 kohnen@em.uni-frankfurt.de | |
| Principal Investigator: prof. T. Kohnen, MD, PhD | |
| Hungary | |
| Semmelweis University | Not yet recruiting |
| Budapest, Hungary, H-1085 | |
| Contact: prof. Z. Nagy, MD, PhD +36 20 825 8468 nagy.zoltan_zsolt@med.semmelweis-univ.hu | |
| Principal Investigator: prof. Z. Nagy, MD, PhD | |
| Italy | |
| Hospital and University of Verona | Not yet recruiting |
| Salo, Italy, 25087 | |
| Contact: prof. R. Bellucci, MD, PhD +39 347 657 5001 roberto.bellucci@ospedaleuniverona.it | |
| Principal Investigator: prof. R. Bellucci, MD, PhD | |
| Netherlands | |
| VU University Medical Center | Not yet recruiting |
| Amsterdam, Netherlands, 1081 HZ | |
| Contact: dr. M van Hecke, MD, PhD +31 20 444 4795 m.vanhecke@vumc.nl | |
| Principal Investigator: dr. M van Hecke, MD, PhD | |
| Regiopraktijk Heerlen, Atrium Medisch Centrum Parkstad | Not yet recruiting |
| Heerlen, Netherlands, 6419 PC | |
| Contact: Rudy MM Nuijts, MD, PhD +31 43 3877344 rudy.nuijts@mumc.nl | |
| Principal Investigator: Rudy MM Nuijts, MD, PhD | |
| University Eye Clinic Maastricht | Not yet recruiting |
| Maastricht, Netherlands, 6202 AZ | |
| Contact: Rudy MM Nuijts, MD, PhD +31 43 3877344 rudy.nuijts@mumc.nl | |
| Contact: Laura HP Wielders, MD +31 43 387 7131 laura.wielders@mumc.nl | |
| Principal Investigator: Rudy MM Nuijts, MD, PhD | |
| Portugal | |
| University Hospital Coimbra | Not yet recruiting |
| Coimbra, Portugal, 3000-075 | |
| Contact: prof. J. Murta, MD, PhD + 351 239 701182 jmurta@huc.min-saude.pt | |
| Principal Investigator: prof. J. Murta, MD, PhD | |
| Russian Federation | |
| S.Fyodorov Eye Microsurgery Complex | Not yet recruiting |
| Moscow, Russian Federation, 127486 | |
| Contact: prof. B. Malyugin, MD, PhD +7 495 488 8511 boris.malyugin@gmail.com | |
| Principal Investigator: prof. B. Malyugin, MD, PhD | |
| Spain | |
| Instituto Microcirurgia Ocular | Not yet recruiting |
| Barcelona, Spain, 08035 | |
| Contact: prof. J. Guell, MD, PhD +34 9325 31500 guell@imo.es | |
| Principal Investigator: prof. J. Guell, MD, PhD | |
| Principal Investigator: | Rudy MM Nuijts, MD, PhD | University Eye Clinic Maastricht, University Hospital Maastricht |
More Information
No publications provided
| Responsible Party: | Maastricht University Medical Center |
| ClinicalTrials.gov Identifier: | NCT01774474 History of Changes |
| Other Study ID Numbers: | NL42463.068.12 |
| Study First Received: | January 7, 2013 |
| Last Updated: | May 13, 2013 |
| Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Keywords provided by Maastricht University Medical Center:
|
Prevention |
Additional relevant MeSH terms:
|
Diabetes Mellitus Edema Macular Edema Cataract Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Signs and Symptoms Macular Degeneration Retinal Degeneration Retinal Diseases Eye Diseases Lens Diseases Dexamethasone acetate Triamcinolone hexacetonide |
Bromfenac Dexamethasone Triamcinolone Triamcinolone Acetonide Dexamethasone 21-phosphate Bevacizumab BB 1101 Triamcinolone diacetate Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 23, 2013