The Efficacy of Empagliflozin on Kidney Functions in Lupus Nephritis Population
Does The Positive Reno-Protective Effect Of Sodium Glucose Co-Transporter 2 Inhibitors Extend To Lupus Nephritis Population?
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.
調査の概要
状態
条件
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Associate professor. Ahmed Yehia
- 電話番号：+20 +201090905827
- メール：ahmed_yehia@med.bsu.edu.eg
研究場所
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Banī Suwayf、エジプト
- 募集
- Beni-suef university Hospital
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コンタクト：
- Associate professor. Ahmed Yehia
- 電話番号：+20 +201090905827
- メール：ahmed_yehia@med.bsu.edu.eg
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副調査官：
- Seif
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：プラセボを 1 日 1 回
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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
他の名前：
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実験的：Empagliflozin 25 mg once daily
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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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Urinary protein-creatinine ratio (UPCR)
時間枠：From recruitment (week 0) to the end of treatment (week 12)
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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.
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From recruitment (week 0) to the end of treatment (week 12)
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Estimated glomerular filtration rate (eGFR)
時間枠：From recruitment (week 0) to the end of treatment (week 12)
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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.
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From recruitment (week 0) to the end of treatment (week 12)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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The tolerance and safety
時間枠：From enrollment (week 0) to 4 weeks following the end of the treatment (week 12)
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The relative risk of adverse events reported between both treatment groups at 4 weeks following the end of the treatment (3 months).
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From enrollment (week 0) to 4 weeks following the end of the treatment (week 12)
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Fasting plasma glucose (FBG)
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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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.
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From enrollment (week 0) to the end of treatment (week 12)
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Systolic (SBP) and diastolic (DBP) blood pressure
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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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.
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From enrollment (week 0) to the end of treatment (week 12)
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Hemoglobin (Hb) level
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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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.
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From enrollment (week 0) to the end of treatment (week 12)
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Hematocrit level
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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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.
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From enrollment (week 0) to the end of treatment (week 12)
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Glycated hemoglobin (HbA1c)
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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The difference in change from baseline in HbA1c to the end of the treatment period (3 months) between study groups
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From enrollment (week 0) to the end of treatment (week 12)
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Adverse events and safety
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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The proportion of adverse events reported in EMPA and placebo groups throughout the research study (3 months).
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From enrollment (week 0) to the end of treatment (week 12)
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Partial response
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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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)
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From enrollment (week 0) to the end of treatment (week 12)
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Body weight
時間枠：From enrollment (week 0) to the end of treatment (week 12)
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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.
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From enrollment (week 0) to the end of treatment (week 12)
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協力者と研究者
スポンサー
出版物と役立つリンク
一般刊行物
- Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
- Herrington WG, Savarese G, Haynes R, Marx N, Mellbin L, Lund LH, Dendale P, Seferovic P, Rosano G, Staplin N, Baigent C, Cosentino F. Cardiac, renal, and metabolic effects of sodium-glucose co-transporter 2 inhibitors: a position paper from the European Society of Cardiology ad-hoc task force on sodium-glucose co-transporter 2 inhibitors. Eur J Heart Fail. 2021 Aug;23(8):1260-1275. doi: 10.1002/ejhf.2286. Epub 2021 Jul 20.
- The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4.
- Piperidou A, Sarafidis P, Boutou A, Thomopoulos C, Loutradis C, Alexandrou ME, Tsapas A, Karagiannis A. The effect of SGLT-2 inhibitors on albuminuria and proteinuria in diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019 Jul;37(7):1334-1343. doi: 10.1097/HJH.0000000000002050.
- McMurray JJV, Wheeler DC, Stefansson BV, Jongs N, Postmus D, Correa-Rotter R, Chertow GM, Greene T, Held C, Hou FF, Mann JFE, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effect of Dapagliflozin on Clinical Outcomes in Patients With Chronic Kidney Disease, With and Without Cardiovascular Disease. Circulation. 2021 Feb 2;143(5):438-448. doi: 10.1161/CIRCULATIONAHA.120.051675. Epub 2020 Nov 13.
- Serenelli M, Bohm M, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, DeMets DL, Bengtsson O, Sjostrand M, Langkilde AM, Anand IS, Chiang CE, Chopra VK, de Boer RA, Diez M, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Verma S, Docherty KF, Jhund PS, McMurray JJV. Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Eur Heart J. 2020 Sep 21;41(36):3402-3418. doi: 10.1093/eurheartj/ehaa496.
- Wheeler DC, Stefansson BV, Batiushin M, Bilchenko O, Cherney DZI, Chertow GM, Douthat W, Dwyer JP, Escudero E, Pecoits-Filho R, Furuland H, Gorriz JL, Greene T, Haller H, Hou FF, Kang SW, Isidto R, Khullar D, Mark PB, McMurray JJV, Kashihara N, Nowicki M, Persson F, Correa-Rotter R, Rossing P, Toto RD, Umanath K, Van Bui P, Wittmann I, Lindberg M, Sjostrom CD, Langkilde AM, Heerspink HJL. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics. Nephrol Dial Transplant. 2020 Oct 1;35(10):1700-1711. doi: 10.1093/ndt/gfaa234.
- McEwan P, Darlington O, McMurray JJV, Jhund PS, Docherty KF, Bohm M, Petrie MC, Bergenheim K, Qin L. Cost-effectiveness of dapagliflozin as a treatment for heart failure with reduced ejection fraction: a multinational health-economic analysis of DAPA-HF. Eur J Heart Fail. 2020 Nov;22(11):2147-2156. doi: 10.1002/ejhf.1978. Epub 2020 Sep 15.
- Leoncini G, Russo E, Bussalino E, Barnini C, Viazzi F, Pontremoli R. SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits. Int J Mol Sci. 2021 Apr 23;22(9):4441. doi: 10.3390/ijms22094441.
- Emmett CJ, Stewart GR, Johnson RM, Aswani SP, Chan RL, Jakeman LB. Distribution of radioiodinated recombinant human nerve growth factor in primate brain following intracerebroventricular infusion. Exp Neurol. 1996 Aug;140(2):151-60. doi: 10.1006/exnr.1996.0125.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- GLIFALN0066
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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