PRevention of Macular EDema After Cataract Surgery (PREMED)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Maastricht University Medical Center
Sponsor:
Collaborator:
European Society of Cataract and Refractive Surgeons
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01774474
First received: January 7, 2013
Last updated: March 5, 2014
Last verified: March 2014
  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
Cystoid 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

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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: July 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: April 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:
  • Yellox
  • Product code: EMEA/H/C/001198
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:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
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:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
n/a
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
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:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
n/a
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
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/Vistrec)

Drug: Bromfenac
n/a
Other Names:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
n/a
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
Drug: Triamcinolone Acetonide
n/a
Other Names:
  • Triesence or Vistrec
  • Product code (NL): RVG 106092
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:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
n/a
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
Drug: Bevacizumab
n/a
Other Names:
  • Avastin
  • Product code: EU/1/04/300/002
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:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
n/a
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
Drug: Bevacizumab
n/a
Other Names:
  • Avastin
  • Product code: EU/1/04/300/002
Drug: Triamcinolone Acetonide
n/a
Other Names:
  • Triesence or Vistrec
  • Product code (NL): RVG 106092

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/Vistrec);
  • 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
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 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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01774474

Contacts
Contact: prof. 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

Locations
Austria
Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus 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 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 Active, not recruiting
Amsterdam, Netherlands, 1081 HZ
Academic Medical Center Not yet recruiting
Amsterdam, Netherlands
Contact: Prof. R Schlingemann, MD, PhD    +31 20 566 3682    r.schlingemann@amc.uva.nl   
Principal Investigator: prof. R. Schlingemann, MD, PhD         
Regiopraktijk Heerlen, Atrium Medisch Centrum Parkstad Recruiting
Heerlen, Netherlands, 6419 PC
Contact: prof. Rudy MM Nuijts, MD, PhD    +31 43 3877344    rudy.nuijts@mumc.nl   
Principal Investigator: prof. Rudy MM Nuijts, MD, PhD         
Eye Hospital Zonnestraal Not yet recruiting
Hilversum, Netherlands
Contact: A. Rulo, MD, PhD    +31 35 772 5561    a.rulo@oogziekenhuiszonnestraal.nl   
Principal Investigator: A Rulo, MD, PhD         
University Eye Clinic Maastricht UMC Recruiting
Maastricht, Netherlands, 6202 AZ
Contact: Prof. 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: Prof. Rudy MM Nuijts, MD, PhD         
Medical Centre Haaglanden Not yet recruiting
the Hague, Netherlands
Contact: M Joosse, MD, PhD    +31 70 330 2937    m.joosse@mchaaglanden.nl   
Principal Investigator: M Joosse, MD, PhD         
St. Elisabeth Hospital Not yet recruiting
Tilburg, Netherlands
Contact: O Goslings, MD, PhD    +31 13 539 8020    o.goslings@elisabeth.nl   
Principal Investigator: O Goslings, 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         
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         
Sponsors and Collaborators
Maastricht University Medical Center
European Society of Cataract and Refractive Surgeons
Investigators
Principal Investigator: prof. 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: March 5, 2014
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
Capsule Opacification
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Lens Diseases
Ophthalmic Solutions
Dexamethasone acetate
Triamcinolone hexacetonide
Bromfenac
Dexamethasone
Triamcinolone
Triamcinolone Acetonide
Dexamethasone 21-phosphate
Bevacizumab
BB 1101
Triamcinolone diacetate
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics

ClinicalTrials.gov processed this record on July 31, 2014