Clinical trial NCT03345901: PROMINENT-Eye Ancillary Study (Protocol AD)
Official title: PROMINENT-Eye Ancillary Study: Diabetic Retinopathy Outcomes in a Randomized Trial of Pemafibrate Versus Placebo (Protocol AD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetic Retinopathy
Diabetic Macular Edema
Keywords: pemafibrate
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Kowa Company, Ltd.
First posted: 2017-11-17
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Despite improved glycemic and systemic control for many patients with diabetes, over the past several decades, diabetic retinopathy (DR) develops and progresses in a large proportion of patients, and visual loss from diabetic eye complications continues to be a leading cause of blindness in the US and other developed countries worldwide. Thus, even a modest ability to prevent DR onset or to slow DR worsening might substantially reduce the number of patients at risk for diabetes-related vision loss worldwide. Widespread use of an oral agent effective at reducing worsening of DR might also decrease the numbers of patients who undergo treatment for DR and diabetic macular edema (DME) and who are consequently at risk for side effects that adversely affect visual function. Two major studies of fenofibrate, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-eye study, have demonstrated clinically important reduction in progression of retinopathy in patients with diabetes assigned to fibrate compared with placebo. However, despite the positive clinical trial results, fenofibrate has not gained wide acceptance as a preventive agent by either ophthalmologists or primary diabetes care providers. Thus, it is important to provide further evidence demonstrating whether or not selectively increasing peroxisome proliferator-activated receptor alpha (PPARα) activity reduces progression of retinopathy in patients with diabetes and non-proliferative diabetic retinopathy at baseline. Pemafibrate is a more potent and selective PPARα modulator than fenofibrate. Its efficacy is currently being evaluated in the Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROMINENT) study for prevention of cardiovascular events in patients with type 2 diabetes. Given the large study cohort with a substantial proportion likely to have DR and the multi-year duration of the PROMINENT trial, this study represents a unique opportunity to assess effects of chronic PPARα activation through pemafibrate therapy on DR outcomes.

Primary Study Objective: To assess whether treatment with pemafibrate (0.2 mg orally BID) compared with placebo reduces the hazard rate of diabetic retinopathy worsening in adults with type 2 diabetes and diabetic retinopathy without neovascularization in at least one eye who are participating in the parent PROMINENT trial.


Eligibility criteria: Inclusion Criteria:

* Already randomized at US or Canadian sites in the PROMINENT study
* Ability to cooperate with dilated ophthalmic examination and imaging procedures
* At least one eye meets the following study eye inclusion criteria:

  1. Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity level between 20 and 53 (minimal to severe non-proliferative diabetic retinopathy (NPDR)), inclusive, on color fundus photographs confirmed by central Reading Center grading.

Exclusion Criteria:

* Study eye exclusion criteria are:

  a. Neovascularization present. b. Current central-involved diabetic macular edema (DME based on optical coherence tomography (OCT) central subfield thickness (CST) i. Zeiss Cirrus: CST ≥ 290µm in women or ≥ 305µm in men ii. Heidelberg Spectralis: CST ≥ 305µm in women or ≥ 320µm in men c. Known major non-diabetic intraocular pathology that in the opinion of the investigator would substantially and adversely affect visual acuity or lead to ocular neovascularization during the course of the study d. Anticipated need for intravitreous anti-vascular endothelial growth factor (VEGF), intravitreous corticosteroid, or pan-retinal photocoagulation (PRP) in the next 6 months following randomization e. History of intravitreous anti-VEGF or corticosteroid treatment within the prior year for any indication.

  f. History of intraocular surgery within prior 4 months or anticipated within the next 6 months following randomization g. Any history of PRP or vitrectomy h. History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to screening i. Aphakia j. Known substantial media opacities that would preclude successful imaging

Primary outcomes:
measure: Diabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome)
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Retina and Vitreous Consultants
state: Arizona
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Glendale
country: United States
facility: Macula & Retina Institute
state: California
city: Huntington Beach
country: United States
facility: Atlantis Eye Care
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Department of Ophthalmology
state: California
city: Long Beach
country: United States
facility: South Coast Retina Center
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates
state: California
city: Westlake Village
country: United States
facility: Retinal Consultants of Southern California Medical Group, Inc.
state: California
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Miami
country: United States
facility: Retina Macula Specialists of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute
state: Florida
city: Pinellas Park
country: United States
facility: Southeast Eye Institute, P.A. dba Eye Associates of Pinellas
state: Florida
city: Sarasota
country: United States
facility: Sarasota Retina Institute
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Augusta
country: United States
facility: Southeast Retina Center, P.C.
state: Georgia
city: Sandy Springs
country: United States
facility: Thomas Eye Group
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago Medical Center
state: Illinois
city: Glenview
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Oak Park
country: United States
facility: Illinois Retina Associates, S.C.
state: Illinois
city: New Albany
country: United States
facility: John-Kenyon American Eye Institute
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Overland Park
country: United States
facility: Mid-America Retina Consultants, P.A.
state: Kansas
city: Shawnee Mission
country: United States
facility: Retina Associates, P.A.
state: Kansas
city: Lexington
country: United States
facility: Retina and Vitreous Associates of Kentucky
state: Kentucky
city: West Monroe
country: United States
facility: Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
state: Louisiana
city: West Monroe
country: United States
facility: Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
state: Louisiana
city: Baltimore
country: United States
facility: Elman Retina Group, P.A.
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Ayer
country: United States
facility: Valley Eye Physicians and Surgeons
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center, University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
state: Michigan
city: Grand Rapids
country: United States
facility: Vitreo-Retinal Associates
state: Michigan
city: Minneapolis
country: United States
facility: Retina Center, PA
state: Minnesota
city: Minneapolis
country: United States
facility: Retina Center, PA
state: Minnesota
city: Saint Louis
country: United States
facility: The Retina Institute
state: Missouri
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: New York
country: United States
facility: MaculaCare
state: New York
city: Rochester
country: United States
facility: Retina Associates of Western New York
state: New York
city: Syracuse
country: United States
facility: Retina-Vitreous Surgeons of Central New York, PC
state: New York
city: Asheville
country: United States
facility: Western Carolina Clinical Research, LLC
state: North Carolina
city: Chapel Hill
country: United States
facility: Kittner Eye Center
state: North Carolina
city: Chapel Hill
country: United States
facility: Kittner Eye Center
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Eye, Ear, Nose and Throat Assoc., PA
state: North Carolina
city: Edmond
country: United States
facility: Retina Vitreous Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute
state: Oklahoma
city: Monroeville
country: United States
facility: Retina Vitreous Consultants
state: Pennsylvania
city: Chattanooga
country: United States
facility: Southeastern Retina Associates
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates, P.C.
state: Tennessee
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: DeSoto
country: United States
facility: Robert E. Torti, MD, PA dba Retina Specialists
state: Texas
city: DeSoto
country: United States
facility: Valley Retina Institute
state: Texas
city: Grapevine
country: United States
facility: Retina Center of Texas
state: Texas
city: Houston
country: United States
facility: Baylor Eye Physicians and Surgeons
state: Texas
city: Houston
country: United States
facility: Baylor Eye Physicians and Surgeons
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston, PA
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
state: Wisconsin
city: Vancouver
country: Canada
facility: UBC/VCHA Eye Care Centre
state: British Columbia
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
Study officials:
affiliation: National Eye Institute (NEI)
name: Emily Chew, MD
role: STUDY_CHAIR
References: