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Trial record 1 of 1 for:    NCT03345901
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PROMINENT-Eye Ancillary Study (Protocol AD)

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ClinicalTrials.gov Identifier: NCT03345901
Recruitment Status : Terminated (recruitment for the substudy did not meet the goals)
First Posted : November 17, 2017
Results First Posted : September 16, 2020
Last Update Posted : September 16, 2020
Sponsor:
Collaborator:
Kowa Company, Ltd.
Information provided by (Responsible Party):
Jaeb Center for Health Research

Tracking Information
First Submitted Date  ICMJE November 7, 2017
First Posted Date  ICMJE November 17, 2017
Results First Submitted Date  ICMJE August 27, 2020
Results First Posted Date  ICMJE September 16, 2020
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE January 15, 2018
Actual Primary Completion Date April 3, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
Diabetic Retinopathy Worsening or Diabetic Macular Edema (DME) Development (Composite Outcome) [ Time Frame: 4 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 14, 2017)
Diabetic retinopathy worsening or diabetic macular edema (DME) development (composite outcome) defined as any of the following: [ Time Frame: 4 years ]
  • For participants with 2 study eyes: 3-step worsening on the Early Treatment Diabetic Retinopathy Study (ETDRS) Retinopathy Severity Scale for Persons at a protocol visit
  • For participants with 1 study eye: 2-step worsening on the ETDRS Retinopathy Severity Scale for Individual Eyes in the study eye at a protocol visit
  • Procedure undertaken for treatment of proliferative diabetic retinopathy at any time including pan-retinal photocoagulation (PRP), intravitreous anti-vascular endothelial growth factor (VEGF), or vitrectomy in either study eye
  • Treatment initiated for treatment of diabetic macular edema (DME) at any time including anti-VEGF, corticosteroids, focal/grid laser, or vitrectomy
  • Development of central-involved DME on OCT with vision loss at 2 or 4-year visit defined as OCT central subfield thickness above machine and gender specific thresholds with at least a 10% increase in thickness from baseline and visual acuity 20/32 or worse (letter score ≤ 78)
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2017)
  • Percentage of participants with 3-step diabetic retinopathy worsening on color photos or receiving treatment for proliferative diabetic retinopathy (PDR) in either eye at any time (irrespective of diabetic macular edema (DME) status or treatment) [ Time Frame: 4 Years ]
  • Percentage of participants with 3-step diabetic retinopathy worsening on color photos [ Time Frame: 4 Years ]
  • Percentage of participants receiving treatment for proliferative diabetic retinopathy (PDR) in either eye at any time [ Time Frame: 4 years ]
  • Percentage of participants that develop central-involved diabetic macular edema (DME) on optical coherence tomography (OCT) with vision loss or receive treatment for DME in either eye at any time (irrespective of diabetic retinopathy status or treatment) [ Time Frame: 4 Years ]
  • Percentage of eyes that develop central-involved diabetic macular edema (DME) on optical coherence tomography (OCT) with vision loss [ Time Frame: 4 years ]
  • Percentage of participants receiving treatment for diabetic macular edema (DME) in either eye at any time [ Time Frame: 4 Years ]
  • Percentage of participants with at least 1, 2 or 3-line losses in visual acuity in either eye [ Time Frame: 4 Years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 14, 2017)
  • Changes from randomization in alanine aminotransferase [ Time Frame: 4 Years ]
    Blood test, change measured in units per liter (U/L)
  • Changes from randomization in aspartate aminotransferase [ Time Frame: 4 Years ]
    Blood test, change from randomization measured in units per liter (U/L)
  • Changes from randomization in creatine kinase [ Time Frame: 4 Years ]
    Blood test, change from randomization measured in units per liter (U/L) or SI Units (mkat/L)
 
Descriptive Information
Brief Title  ICMJE PROMINENT-Eye Ancillary Study (Protocol AD)
Official Title  ICMJE PROMINENT-Eye Ancillary Study: Diabetic Retinopathy Outcomes in a Randomized Trial of Pemafibrate Versus Placebo (Protocol AD)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Diabetic Retinopathy
  • Diabetic Macular Edema
Intervention  ICMJE
  • Drug: Pemafibrate
    0.2 mg orally BID - twice daily
  • Drug: Placebo
    orally BID - twice daily
Study Arms  ICMJE
  • Experimental: Pemafibrate
    .2 mg pemafibrate orally BID
    Intervention: Drug: Pemafibrate
  • Placebo Comparator: Placebo
    Placebo pill orally BID
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 27, 2020)
18
Original Estimated Enrollment  ICMJE
 (submitted: November 14, 2017)
600
Actual Study Completion Date  ICMJE April 3, 2019
Actual Primary Completion Date April 3, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03345901
Other Study ID Numbers  ICMJE DRCR.net Protocol AD
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data related to the eye ancillary study will be made available after completion of the study and publication of the outcome manuscript.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Responsible Party Jaeb Center for Health Research
Study Sponsor  ICMJE Jaeb Center for Health Research
Collaborators  ICMJE Kowa Company, Ltd.
Investigators  ICMJE
Study Chair: Emily Chew, MD National Eye Institute (NEI)
PRS Account Jaeb Center for Health Research
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP