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PRevention of Macular EDema After Cataract Surgery (PREMED)

This study has been completed.
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: April 13, 2017
Last verified: May 2016
  Purpose
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).

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
Intervention Model: Parallel Assignment
Masking: Participant, 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 ]
    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 ]
    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 ]
    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 ]
    Measured using Optical Coherence Tomography (OCT)

  • Intraocular pressure (IOP) as a measurement of safety [ Time Frame: 6 postoperatively ]
    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 ]
    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 ]

    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 ]
    Using OCT

  • Change in macular volume as a measurement of efficacy [ Time Frame: 6 postoperatively ]
    Using OCT

  • Vision-related quality of life as a measurement of efficacy and tolerability [ Time Frame: 12 weeks postoperatively ]
    Using the National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ 25)

  • Cost-effectiveness [ Time Frame: 12 weeks postoperatively ]
    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 ]
    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 ]
    Measured using Optical Coherence Tomography (OCT)

  • Intraocular pressure (IOP) as a measurement of safety [ Time Frame: 12 weeks postoperatively ]
    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 ]

    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 ]
    Using OCT

  • Change in macular volume as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ]
    Using OCT

  • Change in central subfield mean macular thickness as a measurement of efficacy [ Time Frame: 12 weeks postoperatively ]
    Using OCT


Enrollment: 1127
Actual Study Start Date: July 10, 2013
Study Completion Date: November 4, 2016
Primary Completion Date: November 4, 2016 (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
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
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
Other Names:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
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
Other Names:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
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
Other Names:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
Drug: Triamcinolone Acetonide
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
Other Names:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
Drug: Bevacizumab
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
Other Names:
  • Yellox
  • Product code: EMEA/H/C/001198
Drug: Dexamethasone
Other Names:
  • Dexamethasone ophthalmic solution
  • Product code (NL): RVG 56003
Drug: Bevacizumab
Other Names:
  • Avastin
  • Product code: EU/1/04/300/002
Drug: Triamcinolone Acetonide
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 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.

  Eligibility

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Locations
Austria
Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus
Vienna, Austria, A-1140
Hospital of the Brothers of Saint John of God
Vienna, Austria
Belgium
University Hospital Antwerp
Edegem, Belgium, B-2650
Germany
Goethe University
Frankfurt am Main, Germany, 60590
Hungary
Semmelweis University
Budapest, Hungary, H-1085
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HZ
Academic Medical Center
Amsterdam, Netherlands
Amphia Hospital Breda
Breda, Netherlands
Zuyderland Medical Center
Heerlen, Netherlands, 6419 PC
Eye Hospital Zonnestraal
Hilversum, Netherlands
University Eye Clinic Maastricht UMC+
Maastricht, Netherlands, 6202 AZ
Medical Centre Haaglanden
the Hague, Netherlands
St. Elisabeth Hospital
Tilburg, Netherlands
Máxima Medical Center Veldhoven
Veldhoven, Netherlands
Portugal
University Hospital Coimbra
Coimbra, Portugal, 3000-075
Spain
Instituto Microcirurgia Ocular
Barcelona, Spain, 08035
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

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: April 13, 2017

Keywords provided by Maastricht University Medical Center:
Prevention

Additional relevant MeSH terms:
Diabetes Mellitus
Edema
Cataract
Macular Edema
Capsule Opacification
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Signs and Symptoms
Lens Diseases
Eye Diseases
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Dexamethasone acetate
Triamcinolone hexacetonide
Bromfenac
Dexamethasone
Triamcinolone
Triamcinolone Acetonide
Bevacizumab
BB 1101
Triamcinolone diacetate
Ophthalmic Solutions
Tetrahydrozoline
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 16, 2017