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The OPTIMISE Study

Primary Purpose

Pseudophakic Bullous Keratopathy, Fuchs' Endothelial Dystrophy, Intraocular Pressure

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Fluorometholone 0.1% Oph Susp
Dexamethasone 0.1% ophthalmic suspension
Stop steroids
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pseudophakic Bullous Keratopathy focused on measuring Descemet Stripping Endothelial Keratoplasty, Cornea

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: - Patients aged 21 years or older registered on the NOTR as candidates for DMEK corneal transplantation Exclusion Criteria: Inability to complete follow up or comply with study procedures Previous corneal graft in the study eye Known sensitivity or contraindication to the ingredients in the study medications History of uveitis or herpetic keratitis Human Leukocyte Antigen (HLA) typed allograft Pregnancy (current and planned) or lactation Use of other local or systemic immunosuppressive drugs

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Active Comparator

    Experimental

    Active Comparator

    Arm Label

    Intervention STEP I (Year 1 after DMEK)

    Control STEP I (Year 1 after DMEK)

    Intervention STEP II (Year 2 after DMEK)

    Control STEP II (Year 2 after DMEK)

    Arm Description

    Outcomes

    Primary Outcome Measures

    Difference of intraocular pressure elevation between the two arms
    Difference of endothelial cell loss (ECL) compared to pre-surgical baseline between arms

    Secondary Outcome Measures

    Difference of rejection free graft survival between arms
    Differences of patient reported outcome measures between groups
    Differences of incremental cost-effectiveness ratios, including a short term trial-based economic evaluation (TBEE) and a life-long model-based economic evaluation (MBEE)

    Full Information

    First Posted
    January 30, 2023
    Last Updated
    February 7, 2023
    Sponsor
    Maastricht University Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05716945
    Brief Title
    The OPTIMISE Study
    Official Title
    Optimized Immunosuppression for Corneal Transplantation: A Multi-center Randomized Controlled Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 1, 2023 (Anticipated)
    Primary Completion Date
    March 1, 2026 (Anticipated)
    Study Completion Date
    March 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Maastricht University Medical Center

    4. Oversight

    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
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Rationale: The cornea is the most transplanted tissue in the Netherlands, with more than 1,500 procedures performed each year. A minimally invasive technique called Descemet Membrane Endothelial Keratoplasty (DMEK) has become the preferred method in the past decade. The main advantage of DMEK over previous techniques is a low graft rejection rate (1-2% per year). Despite this, rejection prophylaxis after DMEK follows the same high potency regimen as previous techniques in the first year, and patients are burdened with indefinite immunosuppression. The current project, OPTIMISE, aims to establish an evidence-based, cost-effective regimen that effectively prevents rejection and minimizes side effects. Corticosteroid eye drops are the mainstay of ocular immunomodulatory therapy. Their main side effect is a steroid-induced increase in intraocular pressure (IOP). It manifests in about one-fourth of patients within the first year after surgery and can lead to irreversible optic nerve damage and vision loss. Patients with IOP elevation require additional medications and hospital visits resulting in reduced quality of life and increased costs. The optimal dosing regimen in the first year after DMEK and whether patients may safely stop steroids after one year remains unknown. As a result, protocols in the Netherlands vary considerably from surgeon to surgeon. Patients are potentially over-treated in the short and long-term, resulting in undue burden for the patient and increased costs. Consequently, the Dutch Ophthalmology Society (NOG) identified the optimal short- and long-term immunosuppressive protocol for corneal transplantation as one of its Top 10 knowledge gaps, underscoring relevance for clinical practice. With this work, the investigators expect to address this knowledge gap to the benefit of our patients and society. Objective: The OPTIMISE study aims to establish an evidence-based, cost-effective regimen that effectively prevents rejection and minimizes side effects. The hypothesis of this study is that Fluorometholone 0.1% in the first year and discontinuing medication in the second year is a cost-effective treatment strategy after DMEK. Study design: The design of this study is a randomized, controlled multicentre trial with a duration of 24 months. Study population: The study population will consist of 342 patients aged 21 years or older undergoing DMEK surgery in one eye. Intervention: All patients will receive Descemet's Membrane Endothelial Keratoplasty. Following this procedure, patients will be randomized into the following post-operative regime in two stages: STEP-I (Year 1): Control group: DMS 0.1% 6 times a day for 1 month tapered off to once daily within 6 months and then once a day for 6 months. Intervention group: DMS 0.1% 6 times a day for 1 month followed by FML 0.1% 4 times a day for two months tapered off to once daily within four months and then once a day for 6 months. STEP-II (Year 2): Control Group: Half the patients in each study arm will use FML 0.1% daily. Intervention Group: Half the patients in each study arm will discontinue steroids. Main study parameters/endpoints: Primary outcomes: Step-I: IOP elevation compared to baseline Step-II: Endothelial cell loss (ECL) compared to pre-surgical baseline Secondary outcomes are: Rejection free graft survival. Patient reported outcome measures. Incremental cost-effectiveness ratios, including a short term trial-based economic evaluation (TBEE) and a life-long model-based economic evaluation (MBEE) Structural outcomes including corneal, central macular and retinal nerve fibre layer thicknesses, and optic nerve head imaging.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pseudophakic Bullous Keratopathy, Fuchs' Endothelial Dystrophy, Intraocular Pressure
    Keywords
    Descemet Stripping Endothelial Keratoplasty, Cornea

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    342 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Intervention STEP I (Year 1 after DMEK)
    Arm Type
    Experimental
    Arm Title
    Control STEP I (Year 1 after DMEK)
    Arm Type
    Active Comparator
    Arm Title
    Intervention STEP II (Year 2 after DMEK)
    Arm Type
    Experimental
    Arm Title
    Control STEP II (Year 2 after DMEK)
    Arm Type
    Active Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Fluorometholone 0.1% Oph Susp
    Intervention Description
    Year 1: DMS 0.1% 6 times a day for 1 month followed by FML 0.1% 4 times a day for two months tapered off to once daily within four months and then once a day for 6 months. Year 2: Half the patients in each study arm will use FML 0.1% daily.
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone 0.1% ophthalmic suspension
    Intervention Description
    Year 1: DMS 0.1% 6 times a day for 1 month tapered off to once daily within 6 months and then once a day for 6 months.
    Intervention Type
    Other
    Intervention Name(s)
    Stop steroids
    Intervention Description
    Half the patients in each study arm will discontinue steroids.
    Primary Outcome Measure Information:
    Title
    Difference of intraocular pressure elevation between the two arms
    Time Frame
    Year 1
    Title
    Difference of endothelial cell loss (ECL) compared to pre-surgical baseline between arms
    Time Frame
    Year 2
    Secondary Outcome Measure Information:
    Title
    Difference of rejection free graft survival between arms
    Time Frame
    1-2 years
    Title
    Differences of patient reported outcome measures between groups
    Time Frame
    1-2 years
    Title
    Differences of incremental cost-effectiveness ratios, including a short term trial-based economic evaluation (TBEE) and a life-long model-based economic evaluation (MBEE)
    Time Frame
    1-2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    21 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: - Patients aged 21 years or older registered on the NOTR as candidates for DMEK corneal transplantation Exclusion Criteria: Inability to complete follow up or comply with study procedures Previous corneal graft in the study eye Known sensitivity or contraindication to the ingredients in the study medications History of uveitis or herpetic keratitis Human Leukocyte Antigen (HLA) typed allograft Pregnancy (current and planned) or lactation Use of other local or systemic immunosuppressive drugs
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sharista P.G. Baidjnath Panday, MD
    Phone
    +31 6 40186513
    Email
    sharista.baidjnath.panday@mumc.nl

    12. IPD Sharing Statement

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    The OPTIMISE Study

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