PREMED: PRevention of Macular EDema After Cataract Surgery

Sponsor
Maastricht University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT01774474
Collaborator
European Society of Cataract and Refractive Surgeons (Other)
1,127
Enrollment
16
Locations
7
Arms
39.9
Actual Duration (Months)
70.4
Patients Per Site
1.8
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
1127 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
PRevention of Macular EDema After Cataract Surgery
Actual Study Start Date :
Jul 10, 2013
Actual Primary Completion Date :
Nov 4, 2016
Actual Study Completion Date :
Nov 4, 2016

Arms and Interventions

ArmIntervention/Treatment
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
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    Other Outcome Measures

    1. Change in corrected distance visual acuity (CDVA) as a measurement of efficacy [6 postoperatively]

      CDVA measurements will be taken using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts (logMAR).

    2. Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy [6 weeks postoperatively]

      Measured using Optical Coherence Tomography (OCT)

    3. Intraocular pressure (IOP) as a measurement of safety [6 postoperatively]

      IOP (in mmHg) will be measured by Goldmann applanation tonometry

    4. Health-related quality of life as a measurement of efficacy and tolerability [12 weeks postoperatively]

      Using the Health Utility Index mark 3 (HUI-3)

    5. No. of subjects with Adverse Events as a measurement of safety and tolerability [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.

    6. Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy [6 weeks postoperatively]

      Using OCT

    7. Change in macular volume as a measurement of efficacy [6 postoperatively]

      Using OCT

    8. Vision-related quality of life as a measurement of efficacy and tolerability [12 weeks postoperatively]

      Using the National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ 25)

    9. Cost-effectiveness [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.

    10. Change in corrected distance visual acuity (CDVA) as a measurement of efficacy [12 weeks postoperatively]

      CDVA measurements will be taken using ETDRS visual acuity testing charts (logMAR).

    11. Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy [12 weeks postoperatively]

      Measured using Optical Coherence Tomography (OCT)

    12. Intraocular pressure (IOP) as a measurement of safety [12 weeks postoperatively]

      IOP (in mmHg) will be measured by Goldmann applanation tonometry

    13. No. of subjects with Adverse Events as a measurement of safety and tolerability [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.

    14. Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy [12 weeks postoperatively]

      Using OCT

    15. Change in macular volume as a measurement of efficacy [12 weeks postoperatively]

      Using OCT

    16. Change in central subfield mean macular thickness as a measurement of efficacy [12 weeks postoperatively]

      Using OCT

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    SiteCityStateCountryPostal Code
    1Vienna Institute for Research in Ocular Surgery, Hanusch KrankenhausViennaAustriaA-1140
    2Hospital of the Brothers of Saint John of GodViennaAustria
    3University Hospital AntwerpEdegemBelgiumB-2650
    4Goethe UniversityFrankfurt am MainGermany60590
    5Semmelweis UniversityBudapestHungaryH-1085
    6VU University Medical CenterAmsterdamNetherlands1081 HZ
    7Academic Medical CenterAmsterdamNetherlands
    8Amphia Hospital BredaBredaNetherlands
    9Zuyderland Medical CenterHeerlenNetherlands6419 PC
    10Eye Hospital ZonnestraalHilversumNetherlands
    11University Eye Clinic Maastricht UMC+MaastrichtNetherlands6202 AZ
    12Medical Centre Haaglandenthe HagueNetherlands
    13St. Elisabeth HospitalTilburgNetherlands
    14Máxima Medical Center VeldhovenVeldhovenNetherlands
    15University Hospital CoimbraCoimbraPortugal3000-075
    16Instituto Microcirurgia OcularBarcelonaSpain08035

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Maastricht University Medical Center
    ClinicalTrials.gov Identifier:
    NCT01774474
    Other Study ID Numbers:
    • NL42463.068.12
    First Posted:
    Jan 24, 2013
    Last Update Posted:
    Apr 14, 2017
    Last Verified:
    May 1, 2016

    Study Results

    No Results Posted as of Apr 14, 2017