PRevention of Macular EDema After Cataract Surgery

Diabetes Mellitus Clinical Trial

— PREMED  

Official title:

PRevention of Macular EDema After Cataract Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01774474
• Other study ID #: NL42463.068.12
• Status: Completed
• Phase: Phase 3
• First received: January 7, 2013
• Last updated: April 13, 2017
• Start date: July 10, 2013
• Est. completion date: November 4, 2016

Study information

• Verified date: May 2016
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1127
• Est. completion date: November 4, 2016
• Est. primary completion date: November 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Capsule Opacification
• Cataract
• Cystoid Macular Edema
• Diabetes Mellitus
• Edema
• Macular Edema

Intervention

Drug:
• Bromfenac

• Dexamethasone

• Bevacizumab

• Triamcinolone Acetonide

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
Belgium	University Hospital Antwerp	Edegem
Germany	Goethe University	Frankfurt am Main
Hungary	Semmelweis University	Budapest
Netherlands	Academic Medical Center	Amsterdam
Netherlands	VU University 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
Portugal	University Hospital Coimbra	Coimbra
Spain	Instituto Microcirurgia Ocular	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	European Society of Cataract and Refractive Surgeons

Countries where clinical trial is conducted

Austria,  Belgium,  Germany,  Hungary,  Netherlands,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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).	6 postoperatively
Other	Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy	Measured using Optical Coherence Tomography (OCT)	6 weeks postoperatively
Other	Intraocular pressure (IOP) as a measurement of safety	IOP (in mmHg) will be measured by Goldmann applanation tonometry	6 postoperatively
Other	Health-related quality of life as a measurement of efficacy and tolerability	Using the Health Utility Index mark 3 (HUI-3)	12 weeks postoperatively
Other	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; retinal detachment, thrombo-embolic events, endophthalmitis and anterior chamber reactions after intravitreal injections of bevacizumab.	6 weeks postoperatively
Other	Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy	Using OCT	6 weeks postoperatively
Other	Change in macular volume as a measurement of efficacy	Using OCT	6 postoperatively
Other	Vision-related quality of life as a measurement of efficacy and tolerability	Using the National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ 25)	12 weeks postoperatively
Other	Cost-effectiveness	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.	12 weeks postoperatively
Other	Change in corrected distance visual acuity (CDVA) as a measurement of efficacy	CDVA measurements will be taken using ETDRS visual acuity testing charts (logMAR).	12 weeks postoperatively
Other	Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy	Measured using Optical Coherence Tomography (OCT)	12 weeks postoperatively
Other	Intraocular pressure (IOP) as a measurement of safety	IOP (in mmHg) will be measured by Goldmann applanation tonometry	12 weeks postoperatively
Other	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; retinal detachment, thrombo-embolic events, endophthalmitis and anterior chamber reactions after intravitreal injections of bevacizumab.	12 weeks postoperatively
Other	Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy	Using OCT	12 weeks postoperatively
Other	Change in macular volume as a measurement of efficacy	Using OCT	12 weeks postoperatively
Other	Change in central subfield mean macular thickness as a measurement of efficacy	Using OCT	12 weeks postoperatively
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.	6 weeks postoperatively
Secondary	No. of subjects developing clinically significant macular edema as a measurement of efficacy	The secondary endpoint is the occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively.	12 weeks postoperatively