Evidence-Based Evaluation of Naoxintong Capsule in the Treatment of Diabetic Nephropathy With Dampness Retention Pattern: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 410
- 试验地点
- 8
- 主要终点
- Annual Rate of Decline in Estimated Glomerular Filtration Rate (eGFR)
研究概览
简要总结
Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease worldwide and is associated with a high risk of cardiovascular events and mortality. Despite current standard therapies including renin-angiotensin system inhibitors (ACEI/ARB), glycemic control, and blood pressure management, disease progression remains inadequately controlled in many patients.
Naoxintong Capsule is a traditional Chinese medicine formulation composed of 16 herbal ingredients (Astragalus membranaceus, Prunus persica seed, Carthamus tinctorius, Paeonia lactiflora, Angelica sinensis, Ligusticum chuanxiong, Boswellia carterii, Commiphora myrrha, Salvia miltiorrhiza, Achyranthes bidentata, Cinnamomum cassia, Morus alba, Spatholobus suberectus, Buthus martensii, Pheretima aspergillum, and Hirudo nipponica). It has been widely used in China for cardiovascular and cerebrovascular diseases, with demonstrated effects on endothelial protection, anti-inflammation, anti-thrombosis, and plaque stabilization.
This multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of Naoxintong Capsule added to standard conventional therapy in slowing the progression of diabetic nephropathy and providing cardiovascular protection. A total of 410 patients with Type 2 diabetic nephropathy will be randomized (1:1) to receive either Naoxintong Capsules (4 capsules, 3 times daily) or matching placebo, in addition to standard therapy, for 12 months. The primary outcome is the annual rate of decline in estimated glomerular filtration rate (eGFR). Secondary outcomes include changes in proteinuria, CKD stage progression, time to end-stage kidney disease, major adverse cardiovascular events, TCM syndrome scores, and quality of life measures.
详细描述
BACKGROUND AND RATIONALE
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in economically developed countries. China has the largest diabetic population globally, and DN now accounts for approximately 30% of new dialysis patients. Despite the beneficial effects of ACE inhibitors (ACEI) and Angiotensin II receptor blockers (ARB) in the microalbuminuric stage, landmark trials (RENNAL, IDNT, VA NEPHRON-D) have shown that these agents alone or in combination fail to significantly reduce cardiovascular events and all-cause mortality in advanced DN. There is an urgent need for novel therapeutic approaches to slow DN progression and improve survival.
Naoxintong Capsule (National Drug Approval No.: Guoyaozhunzi Z20025001) is a well-established traditional Chinese medicine formulation that has been widely used in China for cardiovascular and cerebrovascular diseases. It comprises 16 herbal and animal-derived ingredients that collectively exert effects through endothelial protection, anti-inflammatory activity, inhibition of thrombosis, and plaque stabilization. Based on the integrative medicine concept of brain-heart-kidney co-treatment and the shared pathophysiological mechanisms underlying DN progression and cardiovascular complications, Naoxintong Capsule represents a promising adjunctive therapy for DN.
STUDY DESIGN AND OBJECTIVES
This is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to provide high-level evidence for the efficacy and safety of Naoxintong Capsule in treating DN. The study will enroll 410 adult patients with confirmed Type 2 diabetic nephropathy across approximately 20 clinical centers in China.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind study. Both the participants and the investigators are blinded to treatment assignment. Naoxintong Capsules and matching placebo capsules are identical in appearance, size, color, packaging, and labeling. The randomization code is maintained by the central data management center and will not be disclosed to investigators or participants until database lock, except in emergency situations requiring unblinding for safety reasons. Emergency unblinding envelopes are provided to each study site.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years.
- •Meets the diagnostic criteria for Type 2 diabetic nephropathy, defined as:
- •Confirmed diagnosis of Type 2 diabetes mellitus; AND
- •At least one of the following: urinary albumin-to-creatinine ratio (UACR) >= 30 mg/g, or eGFR < 60 mL/min/1.73m^2, confirmed by repeat testing (interval >= 3 months), after excluding transient factors such as acute kidney injury, dehydration, infection, or heart failure; OR
- •Renal biopsy confirmed as isolated diabetic nephropathy; AND
- •Exclusion of other primary or secondary kidney diseases.
- •24-hour urinary protein excretion >= 0.5 g and < 3.5 g.
- •Estimated glomerular filtration rate (eGFR) >= 45 mL/min/1.73m^
- •On a stable dose of ACE inhibitor (ACEI) or Angiotensin II receptor blocker (ARB) therapy for at least 8 weeks prior to enrollment. If SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRA), or GLP-1 receptor agonists are being used, the dose must have been stable for at least 4 weeks prior to enrollment and remain unchanged during the study period. Patients not currently using these agents must not initiate them during the study.
- •Signed informed consent form.
排除标准
- •Type 1 diabetes mellitus or other types of diabetes mellitus (e.g., secondary diabetes, maturity-onset diabetes of the young).
- •Coexisting systemic autoimmune or immune-mediated disease where the clinical assessment suggests a non-diabetic nephropathy etiology.
- •Decline in eGFR of > 30% within the past 3 months.
- •Persistent serum potassium > 5.5 mmol/L.
- •Diagnosis of hemorrhagic cardiovascular or cerebrovascular disease within the past 3 months.
- •Known allergy or hypersensitivity to any component of Naoxintong Capsule or placebo; pregnant or lactating women.
- •Participation in another drug or medical device clinical trial within the past 6 months.
- •Any other condition that, in the investigator's judgment, renders the patient unsuitable for participation in the clinical trial (e.g., severe hepatic dysfunction, life expectancy < 1 year).
研究组 & 干预措施
Naoxintong Capsule Group
Participants will receive Naoxintong Capsules (4 capsules per dose, 3 times daily, orally, 30-60 minutes after meals) in addition to standard conventional therapy for diabetic nephropathy, for a total treatment duration of 12 months. Standard conventional therapy includes glycemic control (oral hypoglycemic agents and/or insulin), blood pressure management (ACEI or ARB, with optional non-RASI antihypertensives), lipid-lowering therapy (statins as indicated), dietary management (protein 0.6-0.8 g/kg/day, sodium <3 g/day), and treatment of CKD-related complications as clinically indicated.
干预措施: Naoxintong Capsule (Drug)
Placebo Group
Participants will receive matching placebo capsules (4 capsules per dose, 3 times daily, orally, 30-60 minutes after meals) in addition to standard conventional therapy for diabetic nephropathy, for a total treatment duration of 12 months. Standard conventional therapy is identical to that provided in the Naoxintong group.
干预措施: Placebo (Drug)
结局指标
主要结局
Annual Rate of Decline in Estimated Glomerular Filtration Rate (eGFR)
时间窗: Baseline to Month 12
The annual rate of decline in eGFR (ml/min/1.73m\^2/year), calculated as the slope of eGFR over the 12-month treatment period using all available eGFR measurements at each scheduled visit. eGFR is estimated using the CKD-EPI equation. A less negative slope indicates slower disease progression.
Change in 24-Hour Urinary Protein Excretion From Baseline
时间窗: Baseline to Month 12
Change from baseline in 24-hour urinary protein excretion (g/24h), measured at each scheduled visit. A decrease indicates renal protective effect.
Renal Composite Endpoint: eGFR Decline >30%, ESKD, or MACE
时间窗: From randomization through Month 12
Time to first occurrence of: sustained eGFR decline \>30% from baseline; end-stage kidney disease; or major adverse cardiovascular event.
次要结局
- Proportion of Participants With CKD Stage Improvement, Stabilization, or Progression(Baseline to Month 12)
- Time to Sustained eGFR Decline of Greater Than 30% From Baseline(From randomization through Month 12)
- Time to End-Stage Kidney Disease (ESKD)(From randomization through Month 12)
- Time to First Unplanned Hospitalization for Heart Failure(From randomization through Month 12)
- Time to First Non-Fatal Myocardial Infarction(From randomization through Month 12)
- Time to First Non-Fatal Ischemic Stroke(From randomization through Month 12)
- Time to Cardiovascular Death or Stroke-Related Death(From randomization through Month 12)
- Time to All-Cause Death(From randomization through Month 12)
- Change in TCM Syndrome Score From Baseline(Baseline to Month 12)
研究者
Chen Xiangmei
Professor
Chinese PLA General Hospital