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Combined Ranibizumab and Iluvien for Diabetic Macular Oedema (CASSIE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03784443
Recruitment Status : Withdrawn (Funder withdrawn funding.)
First Posted : December 21, 2018
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

This trial investigated whether adding Iluvien sustained release steroid intravitreal eye implant at the beginning of regular anti-VEGF (anti Vascular Endothelial Growth Factor) intravitreal eye injection treatment for diabetic macular oedema would improve disease stability and reduce the need for regular anti-VEGF intravitreal eye injections over first two years. Diabetic macular oedema, accumulation of microscopic fluid at the back of the eye, is a major cause of poor vision in patients with diabetes.

This is a double mask randomized control multisite trial, to be conducted at 10 NHS hospital eye clinics in England.


Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Diabetes Drug: Iluvien 0.19 MG Drug Implant Drug: Ranibizumab Injection [Lucentis] Procedure: Sham Intravitreal Injection Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double masking randomized control trial with 2 parallel treatment arms: intervention (Iluvien plus Ranibizumab) vs control (Sham plus Ranibizumab)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

To maintain double-masking, participants assigned to the control arm will receive sham implantation. This will be performed with an empty Luer Lock Syringe without a needle attached to it, that will not penetrate the eye nor deliver any drug.

The Iluvien and the sham injection should be performed by the unmasked investigator. The unmasked investigator should not be involved in any patient assessment in the study.

Primary Purpose: Treatment
Official Title: Combined Anti-VEGF Intravitreal Injections With Sustained Steroid Implantation for the Treatment of Diabetic Macular Oedema
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : September 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Active Comparator: Iluvien Arm
Participants assigned to the Iluvien treatment arm will receive Iluvien 0.19 MG Drug Implant to the study eye under aseptic condition at baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
Drug: Iluvien 0.19 MG Drug Implant
Fluocinolone Acetonide Sustained Release Intravitreal Implant at Baseline Visit
Other Name: Fluocinolone Acetonide Implant

Drug: Ranibizumab Injection [Lucentis]
Monthly PRN intravitreal injections
Other Name: Lucentis

Sham Comparator: Control Arm
To maintain double-masking, participants assigned to the control arm will receive Sham Intravitreal Injection at the baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
Drug: Ranibizumab Injection [Lucentis]
Monthly PRN intravitreal injections
Other Name: Lucentis

Procedure: Sham Intravitreal Injection
Sham injection without penetrating needle and without drug delivery at baseline visit.
Other Name: Sham Injection with Luer Lock Syringe




Primary Outcome Measures :
  1. Number of Lucentis Injections received in the study eye [ Time Frame: 24 months ]
    The total number of Lucentis injections needed over 24 months following the intravitreal injection PRN protocol


Secondary Outcome Measures :
  1. Change in visual acuity [ Time Frame: Month 24 ]
    Change in ETDRS (Early Treatment of Diabetic Retinopathy Study) best corrected visual acuity from baseline to month 24

  2. Maintaining at least 20/40 vision [ Time Frame: Month 24 ]
    Percentage of patients that achieve or maintain 20/40 vision

  3. Proportion of participants with vision loss [ Time Frame: Month 24 ]
    Proportion of participants losing 5, 10, 15 ETDRS letters or more

  4. Proportion of participants with visual gain [ Time Frame: Month 24 ]
    Proportion of participants gaining at least 5, 10, 15 ETDRS letters or more

  5. Stability of vision [ Time Frame: Over 24 months ]
    Stability of visual acuity over 24 months using Area Under Curve Analysis (AUC)

  6. Central retinal thickness [ Time Frame: Month 24 ]
    Central retinal thickness (CRT) change as measured by Spectral Domain OCT

  7. CRT stability [ Time Frame: Over 24 months ]
    Stability of CRT over 24 months using AUC analysis

  8. Retinal thickness variability [ Time Frame: Over 24 months ]
    The difference between min and max retinal thickness

  9. Change in Diabetic Retinopathy Severity [ Time Frame: Between baseline and month 24 ]
    Measured using the ETDRS DRSS (Diabetic Retinopathy Severity Score)

  10. Number of focal laser treatments [ Time Frame: Over 24 months ]
    Number of focal laser treatments



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

General

  1. Willingness and the ability to provide informed consent.
  2. Ability and willingness to undertake all scheduled visits, assessment and treatment.
  3. Age 18 years or above.
  4. Documented diagnosis of diabetes mellitus (Type I or Type II) as per WHO (World Health Organization) criteria.
  5. Current regular use of oral anti-hyperglycaemia or insulin therapy.
  6. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year during the study duration of 24 months.

Ocular

  1. Macular thickening due to Diabetic Macular Oedema (DMO) involving the centre of fovea as measured by Spectral Domain OCT with CRT of at least 400 microns.
  2. DMO confirmed by clinical examination and fundus fluorescein angiography.
  3. BCVA between 73 to 25 letters inclusive (Snellen equivalent to 6/12 to 6/96) as measured using ETDRS protocol at 4 meters.
  4. Pseudophakia in the study eye.
  5. Adequate ocular media clarity and pupillary dilatation allowing for posterior segment examination and OCT scanning.

Exclusion Criteria:

General

  1. Cerebral vascular accident, transient ischaemic attack or myocardial infarction within 3 months prior to day 1 (baseline).
  2. Pregnancy or breastfeeding, or intention to become pregnant during the study.
  3. Participation in an investigational trial involving treatment with any drug or devices within 3 months prior to day 1 (baseline) and must not be enrolled in another investigational trial during their participation in this trial.
  4. Systemic anti-VEGF-base therapies within 3 months prior to day 1 (baseline).

Ocular

  1. History of prior intravitreal anti-VEGF therapy or steroid implant in the study eye.
  2. History of proliferative diabetic retinopathy.
  3. History of rubeosis or current rubeosis.
  4. History of neovascularization, tractional retinal detachment, retinal vein occlusion, or significant pre-retinal fibrosis distorting the macular architecture.
  5. History of retinal detachment or macular hole stage 3 or above.
  6. History of vitreoretinal surgery.
  7. Aphakia.
  8. History of glaucoma or uncontrolled ocular hypertension.
  9. Active or suspected ocular or periocular infection or inflammation, including viral diseases of the cornea, conjunctiva and retina, such as active epithelial herpes simplex keratitis (dendritic keratitis), varicella, mycobacterial infections, and fungal diseases.
  10. Panretinal Photocoagulation (PRP) laser treatment within 3 months prior to day 1.
  11. Macular laser (focal or grid) within 3 months prior to day 1.
  12. YAG (yttrium aluminium garnet) laser capsulotomy laser within 3 months prior to day 1.
  13. Any periocular steroid treatment within 6 months prior to day 1.
  14. Cataract operation within 3 months prior to day 1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03784443


Sponsors and Collaborators
Imperial College London
Investigators
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Principal Investigator: Richard Cheong-Leen Imperial College London
Publications:

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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03784443    
Other Study ID Numbers: P78912
First Posted: December 21, 2018    Key Record Dates
Last Update Posted: June 26, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Imperial College London:
Diabetes
Eye
Macular Oedema
Intravitreal Injection
Ranibizumab
Fluocinolone Acetonide
Additional relevant MeSH terms:
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Macular Edema
Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Fluocinolone Acetonide
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists