PRevention of Macular EDema After Cataract Surgery

Phase 3

Completed

• Conditions: Cystoid Macular Edema; Diabetes Mellitus; Cataract
• Interventions: Drug: Bromfenac; Drug: Dexamethasone; Drug: Triamcinolone Acetonide; Drug: Bevacizumab

• Registration Number: NCT01774474
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

Cystoid macular edema (CME) 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. 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).

Detailed Description

The objective of this study is to evaluate the effect of different preventive strategies on the occurrence of CME after cataract surgery in non-diabetic and diabetic patients. The design of the study is a multicentre randomised controlled clinical trial. The study population will consist of 926 non-diabetic patients and 209 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;

* Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose and an intravitreal injection of 1.25 mg bevacizumab;

* 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.

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.

Study Timeline

• Study First Submitted: 2013-01-07
• Study First Submitted QC: 2013-01-21
• Study First Posted: 2013-01-24
• Study Start: 2013-07-10
• Status Verified: 2016-05
• Primary Completion: 2016-11-04
• Study Completion: 2016-11-04
• Last Update Submitted: 2017-04-13
• Last Update Posted: 2017-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1127

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 will be different for non-diabetic and diabetic patients. All ophthalmic exclusion criteria are applicable to the study eye only, unless stated otherwise.

General exclusion criteria for participation in this study are:

1. age below 21 years old;
2. participation in another clinical study;
3. post-traumatic cataract;
4. combined surgery;
5. functional monoculus;
6. previous ocular surgery;
7. progressive glaucoma with severe visual field defects, use of anti-glaucomatous medication or steroid-induced IOP elevation that required IOP-lowering treatment;
8. IOP ≥ 25 mmHg;
9. history of any intraocular inflammation or uveitis;
10. history of pseudoexfoliation syndrome, which is expected to cause peroperative complications;
11. history of Fuchs' endothelial dystrophy or cornea guttata 3+;
12. history of retinal vein occlusion;
13. any macular pathology that might influence VA, other than DME;
14. use of intravitreal bevacizumab or ranibizumab in the previous 6 weeks or intravitreal aflibercept in the previous 10 weeks;
15. use of intra- or periocular corticosteroid injection in the previous 4 months;
16. current use of topical NSAIDs or corticosteroids;
17. use of systemic corticosteroids (≥ 20 mg prednisolone or equivalence);
18. history of relevant adverse events, including serious adverse events (SAE), occurring after administration of NSAIDs, acetylsalicylic acid, sodium sulphite, corticosteroids or bevacizumab;
19. contraindications for use of topical NSAIDs, topical or subconjunctival corticosteroids or intravitreal bevacizumab or related drugs;

Non-diabetic patients with a history of CME will be excluded from participation in the study.

Additionally, diabetic patients will be excluded from participation in case of:

1. macular edema with a CSMT ≥450 µm;
2. very severe NPDR or proliferative DR requiring panretinal photocoagulation or vitrectomy;
3. vitreous haemorrhage present during preoperative visit(s);
4. cerebrovascular accident (CVA), myocardial infarction (MI) or other thromboembolic events in the previous 3 months;
5. a history of recurrent thromboembolic events;
6. a history of severe systemic bleeding in the previous 3 months;
7. major surgery in the previous 3 months;
8. history of glaucoma;

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non diabetics: bromfenac	Bromfenac	bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperatively
Non diabetics: dexamethasone	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
Non diabetics: bromfenac & dexamethasone	Bromfenac	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
Non diabetics: bromfenac & dexamethasone	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
Diabetics: eye drops	Bromfenac	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
Diabetics: eye drops & TA	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 \& a peroperative subconjunctival injection of 40 mg triamcinolone acetonide (TA, Triesence/Vistrec)
Diabetics: eye drops & TA	Triamcinolone Acetonide	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/Vistrec)
Diabetics: eye drops	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
Diabetics: eye drops & TA	Bromfenac	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/Vistrec)
Diabetics: eye drops & bevacizumab	Bromfenac	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)
Diabetics: eye drops & bevacizumab	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 \& a peroperative intravitreal injection of 1.25 mg bevacizumab (Avastin)
Diabetics: eye drops & bevacizumab	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)
Diabetics: eye drops, TA & bevacizumab	Bromfenac	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
Diabetics: eye drops, TA & bevacizumab	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 \& a peroperative subconjunctival injection of 40 mg triamcinolone acetonide (TA) \& a peroperative intravitreal injection of 1.25 mg bevacizumab
Diabetics: eye drops, TA & bevacizumab	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
Diabetics: eye drops, TA & bevacizumab	Triamcinolone Acetonide	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

Primary Outcome Measures

Name	Time	Method
Change in central subfield mean macular thickness as a measurement of efficacy	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.

Secondary Outcome Measures

Name	Time	Method
No. of subjects developing clinically significant macular edema as a measurement of efficacy	12 weeks postoperatively	The secondary endpoint is the occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively.

Trial Locations

Locations (16)

Hospital of the Brothers of Saint John of God; 🇦🇹 Vienna, Austria

University Hospital Antwerp; 🇧🇪 Edegem, Belgium

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus; 🇦🇹 Vienna, Austria

Goethe University; 🇩🇪 Frankfurt am Main, Germany

Semmelweis University; 🇭🇺 Budapest, Hungary

Zuyderland Medical Center; 🇳🇱 Heerlen, Netherlands

Eye Hospital Zonnestraal; 🇳🇱 Hilversum, Netherlands

Amphia Hospital Breda; 🇳🇱 Breda, Netherlands

University Eye Clinic Maastricht UMC+; 🇳🇱 Maastricht, Netherlands

Instituto Microcirurgia Ocular; 🇪🇸 Barcelona, Spain

VU University Medical Center; 🇳🇱 Amsterdam, Netherlands

Medical Centre Haaglanden; 🇳🇱 the Hague, Netherlands

St. Elisabeth Hospital; 🇳🇱 Tilburg, Netherlands

Máxima Medical Center Veldhoven; 🇳🇱 Veldhoven, Netherlands

University Hospital Coimbra; 🇵🇹 Coimbra, Portugal