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

NCT ID: NCT03962296

Last Updated: 2019-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-21
• Study Completion Date: 2015-01-26

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.

Conditions

Diabetic Retinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Entelon

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

Group Type: EXPERIMENTAL

Vitis vinifera extract

Intervention Type: DRUG

Three daily oral doses of 50mg tablets of Vitis vinifera extract(Entelon®, Hanlim Pharm, Seoul, South Korea) were administered to patients in this group

Doxium

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

Group Type: ACTIVE_COMPARATOR

Calcium Dobesilate

Intervention Type: DRUG

Three daily oral doses of 50mg tablets of Calcium Dobesilate(Doxium®, Ilsung Pharm, Seoul, South Korea) were administered to patients in this group

Placebo

Three masking tablets were administered to patients

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets lacked Vitis vinifera extract or calcium dobesilate, but their appearance was identical to those of the study group tablets.

Interventions

Vitis vinifera extract

Three daily oral doses of 50mg tablets of Vitis vinifera extract(Entelon®, Hanlim Pharm, Seoul, South Korea) were administered to patients in this group

Intervention Type: DRUG

Calcium Dobesilate

Three daily oral doses of 50mg tablets of Calcium Dobesilate(Doxium®, Ilsung Pharm, Seoul, South Korea) were administered to patients in this group

Intervention Type: DRUG

Placebo

Placebo tablets lacked Vitis vinifera extract or calcium dobesilate, but their appearance was identical to those of the study group tablets.

Intervention Type: DRUG

Other Intervention Names

Experimental: Entelon; Active comparator:Doxium; Placebo comparator:Placebo

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)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hanlim Pharm. Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Hanyang University

OTHER

Sponsor Role: lead

Responsible Party

Yong Un shin

Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ha kyoung Kim, PhD

Role: PRINCIPAL_INVESTIGATOR

Hallym University Kangnam Sacred Heart Hospital

References

Spadea L, Balestrazzi E. Treatment of vascular retinopathies with Pycnogenol. Phytother Res. 2001 May;15(3):219-23. doi: 10.1002/ptr.853.

Reference Type: RESULT

PMID: 11351356 (View on PubMed)

Other Identifiers

ENTL_501

Identifier Type: -

Identifier Source: org_study_id