PRevention of Macular EDema After Cataract Surgery

NCT ID: NCT01774474

Last Updated: 2017-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-10
• Study Completion Date: 2016-11-04

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.

Conditions

Cystoid Macular Edema; Cataract; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Non diabetics: bromfenac

bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperatively

Group Type: ACTIVE_COMPARATOR

Bromfenac

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Bromfenac

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Bromfenac

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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/Vistrec)

Group Type: ACTIVE_COMPARATOR

Bromfenac

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Triamcinolone Acetonide

Intervention Type: DRUG

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)

Group Type: ACTIVE_COMPARATOR

Bromfenac

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Bromfenac

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Triamcinolone Acetonide

Intervention Type: DRUG

Interventions

Bromfenac

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Triamcinolone Acetonide

Intervention Type: DRUG

Other Intervention Names

Yellox; Product code: EMEA/H/C/001198; Dexamethasone ophthalmic solution; Product code (NL): RVG 56003; Avastin; Product code: EU/1/04/300/002; Triesence or Vistrec; Product code (NL): RVG 106092

Eligibility Criteria

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

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;

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Society of Cataract and Refractive Surgeons

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

prof. Rudy MM Nuijts, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Eye Clinic Maastricht, University Hospital Maastricht

Locations

VU University Medical Center

Amsterdam, , Netherlands

Academic Medical Center

Amsterdam, , Netherlands

Amphia Hospital Breda

Breda, , Netherlands

Zuyderland Medical Center

Heerlen, , Netherlands

Eye Hospital Zonnestraal

Hilversum, , Netherlands

University Eye Clinic Maastricht UMC+

Maastricht, , Netherlands

Medical Centre Haaglanden

The Hague, , Netherlands

St. Elisabeth Hospital

Tilburg, , Netherlands

Máxima Medical Center Veldhoven

Veldhoven, , Netherlands

University Hospital Coimbra

Coimbra, , Portugal

Instituto Microcirurgia Ocular

Barcelona, , Spain

Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus

Vienna, , Austria

Hospital of the Brothers of Saint John of God

Vienna, , Austria

University Hospital Antwerp

Edegem, , Belgium

Goethe University

Frankfurt am Main, , Germany

Semmelweis University

Budapest, , Hungary

Countries

Austria; Belgium; Germany; Hungary; Netherlands; Portugal; Spain

References

Simons RWP, Wielders LHP, Nuijts RMMA, Veldhuizen CA, van den Biggelaar FJHM, Winkens B, Schouten JSAG, Dirksen CD; ESCRS PREMED Study Group. Economic evaluation of prevention of cystoid macular edema after cataract surgery in diabetic patients: ESCRS PREMED study report 6. J Cataract Refract Surg. 2022 May 1;48(5):555-563. doi: 10.1097/j.jcrs.0000000000000785.

Reference Type: DERIVED

PMID: 34417781 (View on PubMed)

Simons RWP, Wielders LHP, Dirksen CD, Veldhuizen CA, van den Biggelaar FJHM, Winkens B, Schouten JSAG, Nuijts RMMA; ESCRS PREMED Study Group. Economic evaluation of prevention of cystoid macular edema after cataract surgery in patients without diabetes: ESCRS PREMED study report 4. J Cataract Refract Surg. 2021 Mar 1;47(3):331-339. doi: 10.1097/j.jcrs.0000000000000449.

Reference Type: DERIVED

PMID: 33009281 (View on PubMed)

Other Identifiers

NL42463.068.12

Identifier Type: -

Identifier Source: org_study_id