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A Multicenter, Randomized, Double-blind Non-inferiority Trial to Evaluate the Efficacy and Safety of Entelon®

Phase 4
Completed
Conditions
Diabetic Retinopathy
Interventions
Registration Number
NCT03962296
Lead Sponsor
Hanyang University
Brief Summary

This was a multicentre, randomised, double-blind controlled study that compared the efficacy and safety of V. vinifera extract, calcium dobesilate (CD), and placebo in subjects with DME. Patients made 6 clinic visits, namely the screening visit; baseline visit (T0); and follow-up visits at 3 (T3), 6 (T6), 9 (T9), and 12 (T12) months.

Detailed Description

Eligible patients were randomised to one of the three study groups in a 1:2:2 ratio (placebo:GSPE:CD group). The randomization schedule was generated and prepared using cubeIWRS® solution (CRScube Inc., Seoul, South Korea, HQ). Randomization was performed using a complete randomization algorithm according to the order of the baseline visit. Subjects took three tablets of a masked study medication three times daily for 12 months; the first dose was taken in the morning of the baseline visit (T0) after baseline assessments were performed, and the last dose was taken in the evening before the month 12 visit (T12). Three daily oral doses of 50mg tablets of GSPE (Entelon®, Hanlim Pharm, Seoul, South Korea) were administered to patients in the GSPE group. Placebo tablets lacked GSPE, but their appearance was identical to that of the study group tablets. Commercially available 250mg CD tablets (Doxium®, Ilsung Pharm, Seoul, South Korea) were used in this study. The identity of the masked study medications was concealed by storing the medications in individually sealed envelopes at the study sites.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
153
Inclusion Criteria
  • Singing a written informed consent prior to selection
  • type 2 DM aged between 40 and 80 years
  • Diabetes is well controlled with drugs for at least 3 months(HbA1c ≤9%)
  • Best-corrected visual acuity over 0.5(20/40) by using ETDRS cisual acuity test
  • Diabetic macular edema with hard exudates CSMT ≤300µm
Exclusion Criteria
  • Lase therapy or intravitreal injection(anti-VEGF, steroid) intraocular surgery within 6 months of enrollment
  • Concomitant macular disease (such as retinal vascular occlusion, choroidal neovascularization, epiretinal membrane, etc)
  • Poor image of optical coherence tomography(signal strength under 50% of narmal value)
  • Concomitant therapy(Kallidinogenase, Vaccinium myrtillus extract, sulodexide)
  • Non-controlled hypertension(systolic pressure >140mmHg or diastolic pressure <90mmHg)
  • Severe renal insufficiency(creatinine >2.2mg/dL, or undergoing dialysis)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EntelonVitis vinifera extractThree daily oral doses of 50mg tablets were administered to patients
DoxiumCalcium DobesilateThree daily oral doses of 250mg tablets were administered to patients
PlaceboPlaceboThree masking tablets were administered to patients
Primary Outcome Measures
NameTimeMethod
The change(Improvement)in the hard exduatesT0(baseline), T12(12months)

The improvement of HE was defined as a decrease in the HE severity by at least two categories of severity at T12 compared with the baseline visit.

Secondary Outcome Measures
NameTimeMethod
The change of Best-corrected visual acuity(BCVA)T0(baseline), T3(3months), T6(6months), T9(9months), T12(12months)

Using the Early Treatment Diabetic Retinopathy Study(ETDRS) protocol

The change of central subfield mean thickness(CSMT)T0(baseline), T3(3months), T6(6months), T9(9months), T12(12months)

Using 6-radial scan protocol or cube scan protocol according to local guidelines of each center;the ETDRS style map

The change of total macular volum(TMV)T0(baseline), T3(3months), T6(6months), T9(9months), T12(12months)

Using 6-radial scan protocol or cube scan protocol according to local guidelines of each center;the ETDRS style map

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