Clinical Trial of Keluoxin Capsules in the Treatment of Diabetic Kidney Disease with Diabetic Retinopathy

A Randomized, Double-blind, Multicenter Clinical Trial of Keluoxin Capsules in the Treatment of Diabetic Kidney Disease with Diabetic Retinopathy

The purpose of the study is to evaluate the efficacy of Keluoxin Capsules for the treatment of diabetic kidney disease (DKD) and diabetic retinopathy (DR) compared to placebo on a conventional treatment basis.

DKD and DR are the main microvascular complications of diabetes mellitus. DKD is currently the leading cause of end-stage renal disease (ESRD), while DR is the leading cause of blindness in the working age population. DKD and DR have similar pathogenesis and pathological manifestations. For patients with DKD whose estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m2, the proportion of patients with mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was 17.38%, 27.57%, 12.29% and 2.28%, respectively. The previous research results showed that Keluoxin Capsules could improve DKD symptoms, reduce proteinuria, protect renal function, and stabilize or improve DR. This study is a multicenter,double-blind, randomized controlled trial. We plan to enroll 460 participants, who will be randomized to receive either Keluoxin capsules(230 cases) or placebo(230 cases) on a conventional treatment basis for 52 weeks.

Inclusion Criteria:

• Age: 18-75 years old, either sex;
• Meeting the diagnostic criteria for type 2 diabetes mellitus and DKD;
• The target eye met the diagnostic criteria for type 2 DR and the fundus showed moderate or severe NPDR;
• Have been treated with an adequate dose of RAASIs for more than 4 weeks;
• The 24h UTP between 0.5g and 3.5g (results of two tests);
• The eGFR ≥30ml/min/1.73m2；
• Blood pressure (BP) ≤ 140/90mmHg;
• Hemoglobin A1c (HbA1c) < 9%;
• Voluntarily sign the informed consent form.

Exclusion Criteria:

• Patients with a known or suspected history of allergy to the test drug and its excipients;

• Various primary kidney diseases or non-diabetic kidney disease as judged by the investigator;

• Heat-toxin syndrome: swelling and pain the throat , redness, swelling, and pain in the eyes, mouth and tongue sores, swollen and painful gums, cough with yellow phlegm, stool stem nod, deep colored urine, red tongue with yellow coating; cold-dampness syndrome: poor appetite, borborygmus, diarrhoea, drowsiness, clear urine in large amounts and high frequency, menstrual disorders, aversion to cold and cold limbs; meet the either manifestation of heat-toxin syndrome or cold-dampness syndrome, that is, the need to be excluded;

• The patient's eye has any of the following conditions:

  1.Target eye (if both eyes of the patient meet the inclusion criteria, the target eye will be determined by the investigator from a medical point of view. In principle, the eye with more severe lesion will be chosen as the target eye, and the eye with clearer refractive media will be chosen if the lesions are of the same degree):

  1. Received periocular corticosteroid injections within 3 months prior to screening;
  2. Use of Chinese patent medicines or chemical drugs with therapeutic effects on DR (e.g., Calcium Dobesilate, Difrarel, Qiming Granules, Shuangdan Mingmu Capsules) within 2 weeks prior to screening;
  3. Suffering from other retinal diseases affecting the macula, e.g. central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), wet age-related macular degeneration (AMD), choroidal neovascularization (CNV), CI-DME, ocular ischemic syndrome, Irvine-Gass syndrome, radiation retinopathy;
  4. Suffering from other eye diseases that affect vision, such as glaucoma, uveitis, optic neuropathy, retinal detachment;
  5. Have undergone the following ophthalmic surgeries or treatments: vitrectomy, macular buckling, glaucoma filtration surgery, panretinal photocoagulation, macular photocoagulation, photodynamic therapy, optic neurotomy, optic nerve sheath fenestration, etc;
  6. Undergone the following eye surgeries within 3 months prior to screening, including cataract surgery and keratoplasty;
  7. The need for cataract surgery during the study period;
  8. Presence of refractive medium opacity and/or pupillary abnormality that affect fundus photography and OCTA imaging; 2. Either eye:
  1. Received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs or corticosteroids within 3 months prior to screening;
  2. Suffering from active inflammation of the eye or periocular area (e.g., hordeolum, infectious conjunctivitis, keratitis, scleritis, endophthalmitis);
  3. Suffering from intraocular or intraorbital space-occupying lesions, and malignancy cannot be excluded.

• Have a history of using systemic glucocorticoids and immunosuppressants within 3 months prior to enrolment;

• Experienced active bleeding within 3 months prior to enrolment;

• The eGFR decreased by ≥ 30% within 3 months prior to enrolment;

• Patients with a history of unilateral or bilateral renal artery stenosis;

• BP < 90/60 mmHg;

• Serious acute complications of diabetes mellitus, serious infections within 4 weeks prior to enrolment;

• Serum albumin (ALB) < 30g/L, hemoglobin ≤ 90g/L;

• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) reaches more than two times of the upper limit of normal level;

• Comorbid with serious diseases of other organs such as cardiovascular disease, respiratory disease, and other serious diseases that may affect the patient's life;

• Patients with malignancy or malignant diseases that affect the overall prognosis;

• Pregnant and lactating women or women with childbearing plans within 6 months;

• Those who have participated in a clinical trial of another drug within 3 months prior to randomization (referring to those who are randomized and treated with the trial drug);

• Others who were judged by the investigator to be inappropriate for inclusion.