Using Calcium Dobesilate to Treat Chinese Patients With Mild to Moderate Non-proliferative Diabetic Retinopathy

Study Overview
=================
Brief Summary
-----------------
Calcium dobesilate has been recommended to treat diabetic retinopathy due to its potential in protecting against retinal vascular damage. However, there was limited evidence exploring its efficacy in combating diabetic retinopathy progression. This study, a single-blind, multicenter, cluster-randomized, controlled superiority trial, was designed to evaluate whether calcium dobesilate could prevent diabetic retinopathy progression into an advanced stage among Chinese patients with mild to moderate non-proliferative diabetic retinopathy.

Detailed Description
-----------------
A total of 1,200 patients with mild to moderate non-proliferative diabetic retinopathy will be enrolled and randomly assigned at a ratio of 1:1 into the control group (that is, conventional treatment group) and the intervention group (that is, conventional treatment plus calcium dobesilate [500 mg, 3 times per day] for 12 months). The severity of diabetic retinopathy will be assessed by the Early Treatment Diabetic Retinopathy Study scale.

Official Title
-----------------
Efficacy of Calcium Dobesilate in Treating Chinese Patients With Mild to Moderate Non-proliferative Diabetic Retinopathy (CALM-DR): a Single-blind, Multicenter, Cluster-randomized, Controlled Trial

Conditions
-----------------
Diabetic Retinopathy

Intervention / Treatment
-----------------
* Drug: Calcium Dobesilate
* Other: conventional treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Being diagnosed with mild to moderate diabetic retinopathy Being older than 18 years Being willing to attend this trial. Exclusion Criteria: Being allergic hypersensitive to experimental drugs or comparator drugs Having alanine aminotransferase or aspartate aminotransferase ≥2 times higher than the upper limit of normal value, or total bilirubin ≥1.5 times higher than the upper limit of normal value upon the exclusion of mild fatty liver disease Having severe renal insufficiency (defined as an estimated glomerular filtration rate ≤30 mL/min/1.73 m^2) Having malignant tumor and some other life-threatening diseases Being in pregnancy, expecting pregnancy, or breast feeding Being with unstable conditions, such as: uncontrolled high blood pressure (e.g., blood pressure >180/100 mmHg); hemoglobin A1c >8.0% or uncontrolled high blood glucose or hypoglycemia; acute cardiovascular events like unstable angina, congestive heart failure, stroke, transient ischemic attack, or myocardial infarction within the previous 3 months; uncontrolled infection; and diabetic ketoacidosis or hyperosmolar state in the past 1 month Being with glaucoma, cataracts, or other opacities that may interfere with retinal examination and fundus photography Receiving laser treatment, cryo-coagulation, or vitrectomy Taking drugs such as diabetic retinopathy or traditional Chinese medicine that may help to improve micro-vascular function in the past 2 weeks Receiving vascular endothelial growth factor therapy in the past 4 months or will be judged to take vascular endothelial growth factor therapy because of disease progression Having attended other clinical trials in the past 1 month, being attending some clinical trials, or some other conditions that were judged unfit for this trial by investigators

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: conventional treatment plus calcium dobesilate<br>maintain lifestyle habits and the usual treatment, plus the use of calcium dobesilate (500 mg, orally, 3 times per day) for 12 months | Drug: Calcium Dobesilate<br>* use calcium dobesilate at the dosage of 500 mg, orally, 3 times per day, for 12 months<br>* Other names: calcium dobesilate use;Other: conventional treatment<br>* maintain lifestyle habits and the usual treatment<br>* Other names: usual care;|
| Active Comparator: conventional treatment group<br>maintain lifestyle habits and the usual treatment for 12 months | Other: conventional treatment<br>* maintain lifestyle habits and the usual treatment<br>* Other names: usual care;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of the progression of diabetic retinopathy | Diabetic retinopathy progression is defined as an increase of 2 or more steps on the Early Treatment Diabetic Retinopathy Study scale during follow-up. | from baseline to the end of treatment (12 months later) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in eyesight | Changes in eyesight assessed by visual chart at 4 m by optometrists | 3-month, 6-month, and 12-month from baseline | 
| Changes in the numbers, location, and types of the retinal lesions | Using retinal photography to detect the changes in the numbers, location, and types of the retinal lesions at different time-points | 3-month, 6-month, and 12-month from baseline | 
| Changes in the retinal blood vessel diameter and arteriovenous ratio | Using photography (optic disc-centered photograph) to detect the retinal blood vessel diameter and arteriovenous ratio at different time-points | 3-month, 6-month, and 12-month from baseline | 
| Changes in metabolic biomarkers such as HbA1c | The metabolic biomarkers were assessed by laboratory measurement at different time-points | 3-month, 6-month, and 12-month from baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
calcium dobesilate, mild to moderate non-proliferative diabetic retinopathy, cluster-randomized controlled trial