Lupus Nephritis (LN)
Conditions
Brief summary
Systemic lupus erythematosis (SLE) is a chronic, most probably auto-immune multisystem disease marked by relapsing-remitting course and the formation of a range of autoantibodies. SLE patients present with serious renal (lupus nephritis (LN)), cardiopulmonary, or nervous manifestation. LN occurs in 40%-70% of SLE cases during the first 10 years of disease and is marked by the presence of proteinuria (hallmark). A novel class of medications had been extracted from phlorizin and indicated for the treatment of type 2 diabetes (T2D), referred to as Sodium glucose cotransporter 2 (SGLT-2) inhibitors. They act by decreasing glucose reabsorption in the proximal renal tubules (SGLT2). Previous studies proved that SGLT2 inhibitors resulted in decreased postprandial hyperglycemia, enhanced glycemic control, reduced body weight and blood pressure, and albuminuria in those with T2D. Large placebo-controlled trials such as Empagliflozin-Kidney (EMPA-Kidney) and Dapagliflozin in Patients with Chronic Kidney Disease (DAPA-CKD) trial demonstrated the efficacy of empagliflozin and dapagliflozin, respectively, in patients with chronic kidney disease (CKD) regardless the diabetic cause of CKD, compared to placebo. EMPA-Kidney with median 2.0 years of follow-up reported that empagliflozin (EMPA) significantly (P\<0.001) lowered (13.1%) the risk of progression of kidney disease and death from cardiovascular causes than placebo (16.9%). Together with, DAPA-CKD trial reported that the risk of a composite of a sustained decline in the estimated GFR of at least 50% was significantly (P\<0.001) lower in the DAPA group (9.2%) compared to placebo group (14.5%) over a median of 2.4 years of follow-up. However, such studies excluded lupus nephritis population from clinical trials. Consequently, an experimental study is conducted to test the hypothesis that SGLT2 inhibitor EMPA is superior to placebo in improving proteinuria and estimated glomerular filtration rate (eGFR) in a group of patients with established LN already receiving the usual standard care and treatment. The trial participants compatabile with the elgibility criteria will be randomly assigned to two groups. One group will take Empagliflozin 25 mg tablet each day along with the standard care therapy. The other group will take a matching placebo besides the usual standard care therapy during the clinical trial period. Study outcomes will be measured three times, one before starting the medical study, the second and third will be 6 and 12 weeks after starting the clinical study, respectively. After that, the statistical siginficance of values between both groups will be reported to test the credibilty of the hypothesis. The study is primarily designed to evaluate the reno-protective effect of EMPA on kidney function, in terms of urinary protein-creatinine ratio (uPCR)and eGFR. Empagliflozin efficacy testing in lupus nephritis population (EMPA-LN) is a prospective, randomized, triple-blinded, parallel-group, placebo controlled phase 4 trial recruiting 66 subjects. A 10% drop-out rate is anticipated based on the clinical opinion of the care provider. The study will be conducted in accordance with the declaration of Helsinki. An ethical approval will be provided from an ethics committee.
Interventions
The intervention includes empagliflozin 25 mg tablet once daily, empagliflozin is a sodium glucose cotransporter-2 inhibitor (SGLT2I) medication that provides a glycemic control, furthermore, it is reported its antiproteinuric effect and improving the kidney function. Each participant randomly assigned to the interventional group will administer one tablet each day provided with the usual standard care therapy within the clinical study period.
The placebo includes a matching tablet similar to empagliflozin tablet in shape, color, and size. Each participant randomly assigned to the Placebo group will administer one tablet each day along with the usual standard medical therapy within the clinical study period
Sponsors
Ahmed Yehia Ismail
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults (≥ 18 years) with established biopsy-proven LN of active III, IV, overlapping III/IV, or overlapping III/V classes. * eGFR ≥ 30 ml.min1.1.73m-2, * Urinary protein creatinine ratio (uPCR) \> 1000 mg/g.
Exclusion criteria
* Subjects with serious hypersensitivity (angioedema and/or anaphylaxis) to EMPA. * eGFR \< 30 ml.min-1.1.73m-2. * uPCR \< 1000 mg/g. * Type 1 or 2 diabetes. * Aterial fibrillation. * Hepatic impairment \[defined as alanine transaminase or aspartate transaminase \>3 times the upper limit of normal (ULN) or total bilirubin \>2 times the ULN at the time of enrolment\]. * Any condition outside the renal and cardiovascular study area with a life expectancy of \< 6 months based on care provider's clinical judgment. * Those who enrolled in an experimental study in the previous 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary protein-creatinine ratio (UPCR) | From recruitment (week 0) to the end of treatment (week 12) | The difference in change in UPCR from baseline to the first follow-up (1.5 months) and to the end of the treatment period (3 months) between both the placebo and EMPA groups. |
| Estimated glomerular filtration rate (eGFR) | From recruitment (week 0) to the end of treatment (week 12) | The difference in change in eGFR from baseline to the first follow-up (1.5 months) and to the end of the treatment period (3 months) between both the placebo and EMPA groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The tolerance and safety | From enrollment (week 0) to 4 weeks following the end of the treatment (week 12) | The relative risk of adverse events reported between both treatment groups at 4 weeks following the end of the treatment (3 months). |
| Fasting plasma glucose (FBG) | From enrollment (week 0) to the end of treatment (week 12) | The difference in change from baseline in FBG to the first follow-up (1.5 months) and to the end of the treatment period (3 months) between study groups. |
| Systolic (SBP) and diastolic (DBP) blood pressure | From enrollment (week 0) to the end of treatment (week 12) | The difference in change from baseline in systolic (SBP) and diastolic blood pressure (DBP) to the first follow-up (1.5 months) and to the end of the treatment period (3 months) between study groups. |
| Hemoglobin (Hb) level | From enrollment (week 0) to the end of treatment (week 12) | The difference in change from baseline in Hb level to the first follow-up (1.5 months) and to the end of the treatment period (3 months) between study groups. |
| Hematocrit level | From enrollment (week 0) to the end of treatment (week 12) | The difference in change from baseline in hematocrit level to the first follow-up (1.5 months) and to the end of the treatment period (3 months) between study groups. |
| Glycated hemoglobin (HbA1c) | From enrollment (week 0) to the end of treatment (week 12) | The difference in change from baseline in HbA1c to the end of the treatment period (3 months) between study groups |
| Adverse events and safety | From enrollment (week 0) to the end of treatment (week 12) | The proportion of adverse events reported in EMPA and placebo groups throughout the research study (3 months). |
| Partial response | From enrollment (week 0) to the end of treatment (week 12) | Proportion of subjects that reach partial renal response in terms of UPCR (defined as ≥ 50% decline in UPCR from baseline value to ˂ 3000 mg/g of creatinine from a 24-h urine collection) |
| Body weight | From enrollment (week 0) to the end of treatment (week 12) | The difference in change from baseline in body weight to 1st follow-up (1.5 months) and to the end of the treatment period (3 months) between study groups. |
Countries
Egypt
Contacts
CONTACTAssociate professor. Ahmed Yehia
Outcome results
None listed