Empagliflozin Reduces Progression of Diabetic Retinopathy in Patients With High Risk of Diabetic Macular Edema

NCT02985242 | Terminated Phase 4

• 2 other identifiers: M16-04EMPA-EYE2016-000825-38
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, active control, two-arm parallel, double-blind, monocenter phase IV clinical trial. The trial compares empagliflozin to glimepiride in patients with type 2 diabetes mellitus in addition to standard of care treatment. Patients with type 2 diabetes mellitus who are between 18 and 80 years of age will be recruited for the clinical trial and randomly allocated to either receive empagliflozin or glimepiride. The assumption of the study is that empagliflozin slows down diabetic retinopathy progression rate and thus a lower microaneurysm formation rate compared to subjects treated with glimepiride by substantially decreased cellular glucotoxicity will be achieved.

Conditions

Diabetes Mellitus, Type II

Outcome Measures

Primary Outcomes (1)

• Microaneurysm formation rate over 12 months, i.e. number of newly developed microaneurysms within 12 months

  Weeks 27 and 52

Secondary Outcomes (13)

• Change in diabetic retinopathy stage (≥ 2 step change on ETDRS severity score)

  Weeks 27 and 52

• Change in microaneurysm count

  Weeks 27 and 52

• Microaneurysm formation rate after 6 months (compared to baseline)

  after 6 months

• Change in retinal thickness (as measured by Optical Coherence Tomography)

  Weeks 27 and 52

• Change in retinal perfusion of microvasculature within the retina (flow in Optical Coherence Tomography Angiography)

  Weeks 27 and 52

Study Arms (2)

Empagliflozin/glimepiride placebo

EXPERIMENTAL

Empagliflozin 25 mg film-coated tablet p.o. daily and glimepiride matching placebo p.o. daily Duration of treatment: 12 months

Drug: Empagliflozin; Drug: Glimepiride placebo

Glimepiride/empagliflozin placebo

ACTIVE COMPARATOR

Glimepiride 2 mg tablet p.o. daily and empagliflozin matching placebo p.o. daily Duration of treatment: 12 months

Drug: Glimepiride; Drug: Empagliflozin placebo

Interventions

Empagliflozin DRUG

Empagliflozin film-coated tablet

Empagliflozin/glimepiride placebo

Glimepiride DRUG

Glimepiride tablet

Glimepiride/empagliflozin placebo

Empagliflozin placebo DRUG

Placebo tablet manufactured to mimic Empagliflozin 25 mg film-coated tablet

Glimepiride/empagliflozin placebo

Glimepiride placebo DRUG

Placebo tablet manufactured to mimic Glimepiride 2 mg tablet

Empagliflozin/glimepiride placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women and men between 18 - 80 years of age
• type 2 diabetes mellitus
• early to moderate stage diabetic retinopathy (ETDRS: 20 (microaneurysms only) to 35 (microaneurysms/ hemorrhages and/or hard exsudates)) in one or both eyes
• stable HbA1c (± 0.5%) for at least 12 weeks
• antidiabetic treatment with either diet, metformin, DPP4, GLP1, pioglitazone, acarbose, or respective combinations
• HbA1c ≥ 6.5 and ≤ 10.0 %
• body mass index \< 46 kg/m2
• either women without childbearing potential defined by:
• at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy
• hysterectomy
• ≥ 50 years and in postmenopausal state \> 1 year
• \< 50 years and in postmenopausal state \> 1 year with serum follicle stimulating hormone (FSH) \> 40 IU/l and serum estrogen \< 30 ng/l or a negative estrogen test, both at screening or women of childbearing potential with a negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of 4 days following the last administration of study medication:
• correct use of one of the following accepted contraception methods: hormonal contraceptives (combined oral contraceptives, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUD/IUS) or a double barrier method, e.g. condom and occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam, gel, film, cream or suppository)
• true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception)
• sexual relationship only with female partners

You may not qualify if:

• Type 1 diabetes
• uncontrolled diabetes mellitus type 2 with fasting glucose \> 13.3 mmol/l confirmed on a second day
• known or suspected hypersensitivity to empagliflozin, glimepiride, or any excipients; and / or known or suspected hypersensitivity to sulfonylureas, sulfonamides or SGLT2 inhibitors in general
• history of multiple severe hypoglycemic episodes within the last two years
• use of Insulin, SGLT2-inhibitor, sulfonylurea derivate or a glinide within past 3 months
• clinical significant macular edema in both eyes and indication for intravitreal anti-VEGF treatment for both eyes at screening or baseline visit. Eyes with a small amount of intraretinal or subretinal fluid (seen in OCT) but no need for intravitreal treatment as judged by the investigator (according to current practice patterns) may be included. Eyes with a history of intravitreal treatment of macular edema which do not need ongoing intravitreal treatment at the time of screening may be included.
• eye diseases or pathologies that prevent clear ophthalmoscopy and evaluation of study parameters, thus not allowing study participation according to the investigator´s judgment, such as (but not only) vitreous hemorrhage, mature cataract, macular pathologies other than diabetic maculopathy
• history of ketoacidosis or metabolic acidosis
• use of loop diuretics
• history of \> 1 urogenital infection/year
• any history of stroke, transient ischemic attack (TIA), instable angina pectoris or myocardial infarction within last 3 months prior to baseline visit
• congestive heart failure New York Heart Association (NYHA) III and IV
• severe valvular or left ventricular outflow obstruction disease needing intervention;
• atrial fibrillation/flutter with a mean ventricular response rate at rest \>100 beats per minute
• chronic lower urinary tract infections (but not simple asymptomatic bacteriuria)

Sponsors & Collaborators

• Hannover Medical School: lead

Study Sites (1)

Hannover Medical School, University Eye Hospital and CRC Core Facility Hannover

Hanover, Lower Saxony, 30625, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Amelie Pielen, MD

  Hannover Medical School, University Eye Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2016
• First Posted: December 7, 2016
• Study Start: June 12, 2017
• Primary Completion: August 1, 2018
• Study Completion: August 16, 2018
• Last Updated: September 27, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)