Does The Positive Reno-Protective Effect Of Sodium Glucose Co-Transporter 2 Inhibitors Extend To Lupus Nephritis Population?
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Urinary protein-creatinine ratio (UPCR)
研究概览
简要总结
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.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Subjects with serious hypersensitivity (angioedema and/or anaphylaxis) to EMPA.
- •eGFR < 30 ml.min-1.1.73m-
- •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.
研究组 & 干预措施
Empagliflozin 25 mg once daily
干预措施: Empagliflozin (25 Mg Tab) along with standard medical therapy (Drug)
Placebo once daily
干预措施: Placebo and standard of care (Drug)
结局指标
主要结局
Urinary protein-creatinine ratio (UPCR)
时间窗: 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)
时间窗: 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.
次要结局
- The tolerance and safety(From enrollment (week 0) to 4 weeks following the end of the treatment (week 12))
- Fasting plasma glucose (FBG)(From enrollment (week 0) to the end of treatment (week 12))
- Systolic (SBP) and diastolic (DBP) blood pressure(From enrollment (week 0) to the end of treatment (week 12))
- Hemoglobin (Hb) level(From enrollment (week 0) to the end of treatment (week 12))
- Hematocrit level(From enrollment (week 0) to the end of treatment (week 12))
- Glycated hemoglobin (HbA1c)(From enrollment (week 0) to the end of treatment (week 12))
- Adverse events and safety(From enrollment (week 0) to the end of treatment (week 12))
- Partial response(From enrollment (week 0) to the end of treatment (week 12))
- Body weight(From enrollment (week 0) to the end of treatment (week 12))
研究者
Ahmed Yehia Ismail
Associate Professor
Beni-Suef University