Dapagliflozin to Reduce the Decline in Renal Function in Patients Newly Diagnosed With Lupus Nephritis (DAPA-LN)
Dapagliflozin Reduces the Progression of Chronic Kidney Disease in Lupus Nephritis: Phase II Trial.
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
**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.
Additionally, cardiovascular-kidney-metabolic health status will be assessed at baseline and at the end of the study using the 2023 American Heart Association classification, to determine improvement, stability, or progression of cardiovascular, renal, and metabolic risk.
The use of other antiproteinuric medications will be allowed at the discretion of the treating physician, except for SGLT2 inhibitors in the control group.
Adverse events and safety outcomes will be monitored throughout the study. If adverse effects or contraindications related to dapagliflozin occur, the medication will be discontinued and appropriate medical care will be provided.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Jalisco
-
Guadalajara, Jalisco, México, 44340
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca".
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- 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) 2019.
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.
Exclusion Criteria:
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 SGLT2. (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. 5. 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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Dapagliflozin Group
Participants in the experimental group will receive a 3-month supply of dapagliflozin 10 mg/day.
During follow-up, primary outcomes will be monitored, including baseline measurements, measurements at 1 month, and measurements at 3 months.
Proteinuria levels, assessed by the urine protein-to-creatinine ratio in a single urine sample or by 24-hour urine protein excretion, and the estimated glomerular filtration rate will be obtained during outpatient visits.
|
Participants in the experimental group will receive a 3-month supply of dapagliflozin 10 mg/day.
During follow-up, baseline measurements of lupus nephritis activity, proteinuria, eGFR, and safety will be assessed at baseline, 1 month, and 3 months.
Otros nombres:
Estimación de los niveles de proteinuria por el índice proteínas/creatinina en muestra única de orina o la cuantificación de proteínas en muestra de orina de 24 horas según corresponda, así como la tasa de filtrado glomerular estimada.
|
|
Sin intervención: Monitoring Group
The follow-up group will receive only standard medical treatment.
During their follow-up, baseline values for lupus nephritis activity, proteinuria, estimated glomerular filtration rate, and safety will be assessed at the start of the study, at one month, and at three months.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
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).
Periodo de tiempo: 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:
|
The monitoring of our overall objective will be evaluated one month and three months after the start of enlistment.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Mónica Vázquez-Del Mercado Espinosa, MD, PhD., Hospital Civil Juan I. Menchaca
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Procesos Patológicos
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedad crónica
- Atributos de la enfermedad
- Enfermedades del tejido conectivo
- Enfermedades autoinmunes
- Enfermedades del sistema inmunológico
- Insuficiencia renal
- Glomerulonefritis
- Nefritis
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades de la piel y del tejido conectivo
- Lupus Eritematoso Sistémico
- Nefritis lúpica
- Insuficiencia Renal Crónica
- Preparaciones farmacéuticas
- Formas de dosificación
- Tabletas
- dapagliflozin
Otros números de identificación del estudio
- CI/00055/2026
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Marco de tiempo para compartir IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
- CÓDIGO_ANALÍTICO
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .