Ignite Creation Date:
2024-05-06 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 2:51 PM
Study NCT ID:
NCT05716945
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-02-10
First Post:
2023-01-30
Brief Title:
The OPTIMISE Study
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
Optimized Immunosuppression for Corneal Transplantation A Multi-center Randomized Controlled Clinical Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Rationale
The cornea is the most transplanted tissue in the Netherlands with more than 1500 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 01 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 Descemets 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 01 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 01 6 times a day for 1 month followed by FML 01 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 01 daily Intervention Group Half the patients in each study arm will discontinue steroids
Main study parametersendpoints
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
The cornea is the most transplanted tissue in the Netherlands with more than 1500 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 01 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 Descemets 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 01 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 01 6 times a day for 1 month followed by FML 01 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 01 daily Intervention Group Half the patients in each study arm will discontinue steroids
Main study parametersendpoints
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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None