Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients

Study Overview
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Brief Summary
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This study aims to assess sodium glucose linked transoprter inhibitors(SGT2i) role in regression of ongoing kidney and cardiac diseases among lupus nephritis patient either diabetic or non-diabetic under different immunosuppressive therapy. The main objective of this study is to: To compare use of sodium glucose linked transoprter inhibitors (SGLT2i) versus standard care in regression of chronic kidney disease in patient with lupus nephritis (LN). To study the safety and efficacy of this drug group with use of immunosuppression and possible interaction. Patients with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 will be randomized into two groups Study group will receive SGLT2i inhibitor as add on drug or replace another drug according to patient clinical situation, Dapagliflozin 10 mg and 25 mg will be used once daily with or without food. Control group will be maintained on placebo.We will follow up all patients for 12 months and compare their results.

Detailed Description
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Study sitting: Nephrology and renal transplant unit at urology and nephrology center in Mansoura University. It will include 100 patients with lupus nephritis, Diagnosis of glomerulonephritis was performed by renal biopsy, and all of the renal biopsies were carried out at urology and nephrology center. Patients with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 will be randomized into two groups Study group will receive SGLT2i inhibitor as add on drug or replace another drug according to patient clinical situation, dapagliflozin 10 mg and 25 mg will be used once daily with or without food. Control group will be maintained on placebo. The primary endpoint will be sustained decline in eGFR ≥50%, ESKD, or kidney or cardiovascular death We will follow up all patients for 12 months and compare their results. 2. Inclusion criteria: Patients aged more than 16 year. Willing to sign informed consent. Diagnosis of Systemic Lupus Erythematosus (SLE) according to american college of rheumatology (ACR) classification criteria. Renal biopsy showed lupus nephritis. Patient with eGFR > 30 ml/min/1.73m2 by cockcroft-gault equation. 3. Exclusion criteria: Patients with eGFR <30 ml/min per 1.73 m2. Current pregnancy or lactation. Medical history of chronic disease (CLD, cancer, severe respiratory distress, gastrointestinal tract lesions). Patients refusing to participate in the study or lost follow up. Evidence of urinary obstruction of difficulty in voiding at screening. Patients who are receiving high dose diuretics or combined Angiotensin converting enzymes inhibitors(ACEI) and Angiotensin II receptor blockers (ARBS). Patients who have frequent hypotensive episode or systolic blood pressure (SBP) <100 mmHg. Operational design: Study Protocol: Patients included in the study will treated with dapaglifilozin initiated at a total daily dosage of 10 mg/kg per day. Study design: Type of the study: randomized controlled study. The following data will be gathered and evaluated for all patients: I-before intervention: Serum creatinine, Creatinine clearance. 24 hour urine protein, urine protein/creatinine ratio. Urine analysis. HBA1c. Hemoglobin (HGB). Uric acid and lipid profile. Lupus serology. II-after intervention: All patients will be evaluated monthly regarding: Serum creatinine, creatinine clearance. 24 hour proteinuria, protein/creatinine ratio. Fasting, random and postprandial glucose levels. calcineurin inhibitors (CNI) trough level if used. Urine analysis. HGB level. Uric acid, lipid profile. Lupus serology. Cardiovascular assessment: Echocardiogram. Atherosclerosis and vascular calcification incidence (NCCT model). Regular measurement of blood pressure each visit ll patients will be evaluated at 12 month regarding: erythropoetin level Hepcidin level.

Official Title
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Study of the Cardio Renal Effects of SGLT2 Inhibitors Among Diabetic and Non-diabetic Lupus Nephritis Patients

Conditions
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SLE, Lupus Nephritis, SGLT2 Inhibitors

Intervention / Treatment
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* Drug: dapagliflozin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged more than 16 year. Willing to sign informed consent. Diagnosis of SLE according to EULAR/ACR classification criteria. Renal biopsy showed lupus nephritis. Patient with eGFR > 30 ml/min/1.73m2 by cockcroft-gault equation. Exclusion Criteria: Patients with eGFR <30 ml/min per 1.73 m2. Current pregnancy or lactation. Medical history of chronic disease (CLD, cancer, severe respiratory distress, gastrointestinal tract lesions). Patients refusing to participate in the study or lost follow up. Evidence of urinary obstruction of difficulty in voiding at screening. Patients who are receiving high dose diuretics or combined ACEI, Angiotensin II receptor blockers (ARBS). Patients who have frequent hypotensive episode or SBP <100 mmHg.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized controlled trial, It will include 100 patients with lupus nephritis, Diagnosis of glomerulonephritis was performed by renal biopsy, and all of the renal biopsies were carried out at urology and nephrology center. Patients with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 will be randomized into two groups Study group will receive SGLT2i inhibitor as add on drug or replace another drug according to patient clinical situation, Dapagliflozin 10 mg and 25 mg will be used once daily with or without food. Control group will be maintained on placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: study group<br>study group: will receive SGLT2i as add on drug or replace another drug according to the patient clinical situation, Dapagliflozin 10 mg will be used once daily with or without food for one ye | Drug: dapagliflozin<br>* The patients will be randomized into two groups Study group: will receive SGLT2i as add on drug or replace another drug according to the patient clinical situation, Dapagliflozin 10 mg will be used once daily with or without food.<br>|
| Active Comparator: control group<br>Control group: will receive placebo as add on drug once daily with or without food for one year. | Drug: placebo<br>* Control group: will be maintained on their medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of dapagliflozin compared to placebo on renal function | Effect of dapagliflozin compared to placebo on eGFR. | 1 year | 
| Cardiovascular assessment in two groups | effect of dapagliflozin compared to placebo on coronary calcification (NCCT model) | 1 year | 
| Effect of dapagliflozin compared to placebo on Erythropoietin level | Erythropoietin level will be measured in two groups before and after intervention | 1 year | 
| Effect of dapagliflozin compared to placebo on hepcidin level | hepcidin level will be measured in two groups before and after intervention | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of dapagliflozin compared to placebo on ECCHO parameters | ECCHO will be done before and after intervention | 1 year | 
| Effect of dapagliflozin compared to placebo on body weight | body weight will be assessed throughout the study | 1 year |