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

Hanyang University

Status and phase: Completed; Phase 4

Conditions: Diabetic Retinopathy

Treatments: Drug: Calcium Dobesilate; Drug: Vitis vinifera extract; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03962296

ENTL_501

Details and patient eligibility

About

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.

Full 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.

Enrollment: 153 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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153 participants in 3 patient groups, including a placebo group

Entelon

Experimental group

Description:

Three daily oral doses of 50mg tablets were administered to patients

Treatment:

Drug: Vitis vinifera extract

Doxium

Active Comparator group

Description:

Three daily oral doses of 250mg tablets were administered to patients

Treatment:

Drug: Calcium Dobesilate

Placebo

Placebo Comparator group

Description:

Three masking tablets were administered to patients

Treatment:

Drug: Placebo