Clinical trial NCT03962296: A Multicenter, Randomized, Double-blind Non-inferiority Trial to Evaluate the Efficacy and Safety of Entelon®
Official title: A Multicenter, Randomized, Double-blind Non-inferiority Trial to Evaluate the Efficacy and Safety of Entelon® as Compared to Doxium Tab. And Placebo for the Treatment of Nonproliferative Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Retinopathy
Keywords: Diabetic retinopathy, hard exudates
Lead sponsor: Hanyang University
Sponsor class: OTHER
Collaborators: name: Hanlim Pharm. Co., Ltd.
First posted: 2019-05-24
Enrollment: 153
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: The change(Improvement)in the hard exduates
timeFrame: T0(baseline), T12(12months)
Secondary outcomes:
measure: The change of Best-corrected visual acuity(BCVA)
timeFrame: T0(baseline), T3(3months), T6(6months), T9(9months), T12(12months)
measure: The change of central subfield mean thickness(CSMT)
timeFrame: T0(baseline), T3(3months), T6(6months), T9(9months), T12(12months)
measure: The change of total macular volum(TMV)
timeFrame: T0(baseline), T3(3months), T6(6months), T9(9months), T12(12months)
Other outcomes:
Locations:
Study officials:
affiliation: Hallym University Kangnam Sacred Heart Hospital
name: Ha kyoung Kim, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spadea L, Balestrazzi E. Treatment of vascular retinopathies with Pycnogenol. Phytother Res. 2001 May;15(3):219-23. doi: 10.1002/ptr.853.