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.
Studieoversikt
Status
Forhold
Studietype
Registrering (Antatt)
Fase
- Fase 4
Kontakter og plasseringer
Studiekontakt
- Navn: Associate professor. Ahmed Yehia
- Telefonnummer: +20 +201090905827
- E-post: ahmed_yehia@med.bsu.edu.eg
Studiesteder
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Banī Suwayf, Egypt
- Rekruttering
- Beni-suef university Hospital
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Ta kontakt med:
- Associate professor. Ahmed Yehia
- Telefonnummer: +20 +201090905827
- E-post: ahmed_yehia@med.bsu.edu.eg
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Underetterforsker:
- Seif
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Placebo komparator: Placebo én gang daglig
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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
Andre navn:
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Eksperimentell: 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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Urinary protein-creatinine ratio (UPCR)
Tidsramme: 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)
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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The tolerance and safety
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Sponsor
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Urogenitale sykdommer
- Mannlige urogenitale sykdommer
- Nyresykdommer
- Urologiske sykdommer
- Kvinnelige urogenitale sykdommer
- Kvinnelige urogenitale sykdommer og graviditetskomplikasjoner
- Bindevevssykdommer
- Autoimmune sykdommer
- Sykdommer i immunsystemet
- Glomerulonefritt
- Lupus erythematosus, systemisk
- Nefritt
- Hud- og bindevevssykdommer
- Lupus nefritis
- Health Services Administration
- Helsevesenets kvalitet, tilgang og evaluering
- Farmasøytiske preparater
- Doseringsformer
- Kvalitet på helsehjelpen
- Kvalitetsindikatorer, helsehjelp
- Standard for omsorg
- Empagliflozin
- Tabletter
Andre studie-ID-numre
- GLIFALN0066
Plan for individuelle deltakerdata (IPD)
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