Dapagliflozin Reduces the Progression of Chronic Kidney Disease in Lupus Nephritis: Phase II Trial.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Definition of renal remission in lupus nephritis proposed by the KDIGO 2024 guideline (Kidney Disease: Improving Global Outcomes, Clinical practice guideline for the management of lupus nephritis).
研究概览
简要总结
Lupus nephritis is one of the most serious complications of lupus, an autoimmune disease in which the immune system mistakenly attacks the body's own tissues. This condition causes inflammation and damage to the kidneys and is a major cause of chronic kidney disease, especially in the Latin American population. In these patients, the disease often appears at a younger age, presents with more intense inflammation, and has a more aggressive course.
Although treatments exist that help control the immune response and reduce kidney damage, a significant proportion of patients do not achieve sustained kidney recovery. As a result, protein loss in the urine persists, and kidney function continues to deteriorate over time.
Given this situation, new therapeutic alternatives have emerged aimed at protecting kidney function. Among them is dapagliflozin, a medication that has shown benefits in various types of chronic kidney disease by helping to lower pressure within the kidneys, reduce inflammation, and limit the formation of scar tissue. However, there is still limited information on its effectiveness in people with active lupus nephritis.
The objective of this study is to evaluate the efficacy and safety of dapagliflozin in preventing the progression of chronic kidney disease in patients with lupus nephritis. The results will generate scientific evidence to help improve renal protection strategies in this population.
To this end, a phase II, open-label, controlled, randomized clinical trial will be conducted in adult patients newly diagnosed with lupus nephritis treated at the Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". Participants will be randomly assigned in a one-to-one ratio to two groups: one will receive standard treatment plus dapagliflozin (10 mg daily), and the other will receive only standard treatment.
For three months, the amount of protein excreted in urine, renal function, and progression to chronic kidney disease will be evaluated. In addition, potential adverse effects, changes in lupus activity, and variables related to the prevention of cardiovascular, renal, and metabolic diseases will be recorded.
详细描述
**Description of Procedures**
Participants who meet the inclusion and exclusion criteria and provide written informed consent will be randomly assigned in a 1:1 ratio to one of two study groups: standard treatment plus dapagliflozin 10 mg/day or standard treatment alone.
Participants in the intervention group will receive a three-month supply of dapagliflozin (84 tablets). All participants will continue routine outpatient follow-up for a period of three months.
The primary evaluation will include baseline and 3-month measurements of proteinuria (using either the urine protein-to-creatinine ratio in a spot urine sample or 24-hour urine protein quantification) and kidney function assessed by estimated glomerular filtration rate (eGFR). These laboratory tests are part of the standard clinical monitoring of patients with lupus nephritis.
Renal response will be classified according to the KDIGO 2024 recommendations as complete remission, primary renal response, partial response, or no response, based on changes in proteinuria and kidney function during follow-up.
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
- None
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
- •Patients over 18 years of age.
- •Patients who agree to participate in the study after signing an informed consent form.
- •Patients who meet the classification criteria for systemic lupus erythematosus proposed by the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR)
- •Patients diagnosed with active lupus nephritis based on one or a combination of the following:
- •- Renal biopsy: based on a report of the following histological classes: I, II, III, IV, V, or mixed (combinations of the aforementioned classes), following the recommendations of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis and modified National Institutes of Health (ISN/RPS) 2018 (Appendix 1). -Clinical: diagnostic variables of renal domain activity according to the SELENA-SLEDAI or Mex-SLEDAI composite clinical criteria (Appendix 2), with proteinuria always estimated on more than two occasions.
- •Patients with proteinuria greater than 500 mg/dL per day, quantified by the protein/creatinine ratio in a single urine sample or by quantification of protein in a 24-hour urine collection.
排除标准
- •1. Pacientes con diagnóstico por biopsia o a integración del clínico de nefritis lúpica con temporalidad mayor a 6 meses.
- •2. Pacientes bajo tratamiento actual con algún inhibidor iSGLT2, sulfonilureas, bombas de infusión continua de insulina.
- •3. Pacientes con contraindicación del uso de inhibidor SGLT
- •(Estadio clínico de enfermedad renal crónica KDIGO IV o tasa de filtrado glomerular estimada <20 ml/min, estado de deshidratación moderado a severo, sospecha de infección grave aguda, requerimiento de evento quirúrgico en días próximos. Infecciones del tracto urinario o genitales severas, recurrentes (>3 eventos/año), o con uso de dispositivos urinarios permanentes.
- •4. Pacientes en embarazo en curso, puerperio o lactancia.
- •Paciente con requerimiento de reanimación hídrica agresiva, uso de aminas vasoactivas, requerimiento de dispositivos de ventilación mecánica invasiva o de alto flujo, terapias de sustitución orgánica, falla orgánica múltiple, infección grave o complicada, o cualquier estado patológico que por criterio clínico se considere al paciente como crítico.
- •6. Estado de acidosis metabólica (por gasometría venosa pH <7.30) o sospecha de cetoacidosis euglucémica.
- •7. Pacientes con diagnóstico previo de Diabetes Mellitus tipo 1, tipo 2 o con el reporte al tamizaje de HbA1c > 6.5%, glucemia en ayuno ≥126 mg/dL o glucemia ≥200 mg/dL asociado a síntomas de hiperglucemia.
- •8. TFGe <20 mL/min o requerimiento de terapia de sustitución renal previa o inminente.
结局指标
主要结局
Definition of renal remission in lupus nephritis proposed by the KDIGO 2024 guideline (Kidney Disease: Improving Global Outcomes, Clinical practice guideline for the management of lupus nephritis).
时间窗: The monitoring of our overall objective will be evaluated one month and three months after the start of enlistment.
The following variables and definitions of remission in lupus nephritis will be reported: * Complete: Reduction of proteinuria to \<500 mg/dL. Stabilization or improvement of the estimated glomerular filtration rate (eGFR) (10-15% of baseline). * Primary renal response: Proteinuria \<700 mg/dL. No worsening of the eGFR \>20% of baseline or greater than 60 mL/min/1.73 m². No use of rescue therapy. * Partial: Reduction of proteinuria by at least 50% to \<3,000 g/dL and stabilization or improvement of the eGFR (10-15% of baseline). * No renal response: Failure to achieve any of the above definitions within 3 months.
次要结局
未报告次要终点
研究者
Mónica Vazquez-Del Mercado
Coordinator PANLAR Myositis Study Group. Coordinator of the Jalisco Regional Chapter of the National Academy of Medicine of Mexico Full Member of the National Academy of Medicine Mexico SNII Level 3, SECIHTI Director of the Institute for Research in
Hospital Civil Juan I. Menchaca