Rationale and study design of a randomized controlled trial to investigate the renoprotective effect of canagliflozin assessed by test of renal hemodynamics in diabetic kidney disease (the FAGOTTO study).
Canagliflozin
Clinical trial
Diabetic kidney disease
Renal hemodynamics
Renoprotection
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
received:
25
09
2022
accepted:
20
07
2023
medline:
7
8
2023
pubmed:
4
8
2023
entrez:
3
8
2023
Statut:
epublish
Résumé
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are considered to have the potential to maintain renal function by correcting glomerular hypertension in patients with diabetic kidney disease (DKD). The aim of this study is to demonstrate the renoprotective effect of SGLT2i by measuring renal hemodynamics, including glomerular filtration fraction (FF), in type 2 diabetic patients with moderate renal dysfunction. Renoprotective effect of canagliflozin derived from test of renal hemodynamics in diabetic kidney disease (FAGOTTO) study is a 12-week multicenter, open-label, randomized (1:1), parallel-group trial of type 2 diabetic patients with diabetic kidney disease (30 ≤ estimated glomerular filtration rate [eGFR] ≤ 60 mL/min/1.73 m The FAGOTTO study will elucidate the mechanism of the renoprotective action of SGLT2i. The background, rationale, and study design of this trial are presented. To date, > 80 patients have been enrolled in this trial. The study will end in 2025. jRCT (Japan Registry Of Clinical Trials) jRCTs041200069. Date of registration: November 27, 2020.
Sections du résumé
BACKGROUND
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are considered to have the potential to maintain renal function by correcting glomerular hypertension in patients with diabetic kidney disease (DKD). The aim of this study is to demonstrate the renoprotective effect of SGLT2i by measuring renal hemodynamics, including glomerular filtration fraction (FF), in type 2 diabetic patients with moderate renal dysfunction.
METHODS
Renoprotective effect of canagliflozin derived from test of renal hemodynamics in diabetic kidney disease (FAGOTTO) study is a 12-week multicenter, open-label, randomized (1:1), parallel-group trial of type 2 diabetic patients with diabetic kidney disease (30 ≤ estimated glomerular filtration rate [eGFR] ≤ 60 mL/min/1.73 m
DISCUSSION
The FAGOTTO study will elucidate the mechanism of the renoprotective action of SGLT2i. The background, rationale, and study design of this trial are presented. To date, > 80 patients have been enrolled in this trial. The study will end in 2025.
TRIAL REGISTRATION
jRCT (Japan Registry Of Clinical Trials) jRCTs041200069. Date of registration: November 27, 2020.
Identifiants
pubmed: 37537531
doi: 10.1186/s12882-023-03277-0
pii: 10.1186/s12882-023-03277-0
pmc: PMC10401745
doi:
Substances chimiques
Canagliflozin
0SAC974Z85
Sodium-Glucose Transporter 2 Inhibitors
0
Banques de données
JPRN
['jRCTs041200069']
Types de publication
Randomized Controlled Trial
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
228Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
International Diabetes Federation. IDF Diabetes Atlas. 9th ed. 2019.
Ministry of Health, Labour and Welfare, Japan. Labour and Welfare. 2019.
American Diabetes A. 11. Microvascular complications and foot care: standards of medical care in diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S151-67.
doi: 10.2337/dc21-S011
Cheng HT, Xu X, Lim PS, Hung KY. Worldwide epidemiology of diabetes-related end-stage renal disease, 2000–2015. Diabetes Care. 2021;44(1):89–97.
doi: 10.2337/dc20-1913
pubmed: 33203706
Kosaku Nitta SG, Ikuto Masakane, Norio Hanafusa, Masatomo Taniguchi, Takeshi Hasegawa, Shigeru Nakai, Atsushi Wada, Takayuki Hamano, Junichi Hoshino, Nobuhiko Joki, Masanori Abe, Keiichi Yamamoto & Hidetomo Nakamoto on behalf of the Japanese Society for Dialysis Therapy Renal Data Registry Committee: Annual dialysis data report for 2018, JSDT Renal Data Registry: survey methods, facility data, incidence, prevalence, and mortality. Ren Replace Ther. 2020;6. https://doi.org/10.1186/s41100-020-00286-9 .
Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ, Lee BJ, Perkins RM, Rossing P, Sairenchi T, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012;380(9854):1662–73.
doi: 10.1016/S0140-6736(12)61350-6
pubmed: 23013602
pmcid: 3771350
Scheen AJ. Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16(10):556–77.
doi: 10.1038/s41574-020-0392-2
pubmed: 32855502
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.
doi: 10.1056/NEJMoa1504720
pubmed: 26378978
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34.
doi: 10.1056/NEJMoa1515920
pubmed: 27299675
Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587–97.
doi: 10.1161/CIRCULATIONAHA.113.005081
pubmed: 24334175
van Bommel EJM, Muskiet MHA, van Baar MJB, Tonneijck L, Smits MM, Emanuel AL, Bozovic A, Danser AHJ, Geurts F, Hoorn EJ, et al. The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. Kidney Int. 2020;97(1):202–12.
doi: 10.1016/j.kint.2019.09.013
pubmed: 31791665
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92.
doi: 10.1053/j.ajkd.2008.12.034
pubmed: 19339088
Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Furtado RHM, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31–9.
doi: 10.1016/S0140-6736(18)32590-X
pubmed: 30424892
Zinman B, Inzucchi SE, Lachin JM, Wanner C, Ferrari R, Fitchett D, Bluhmki E, Hantel S, Kempthorne-Rawson J, Newman J, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME). Cardiovasc Diabetol. 2014;13:102.
doi: 10.1186/1475-2840-13-102
pubmed: 24943000
pmcid: 4072621
Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Stein P, Desai M, Shaw W, Jiang J, Vercruysse F, et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)–a randomized placebo-controlled trial. Am Heart J. 2013;166(2):217-223.e211.
doi: 10.1016/j.ahj.2013.05.007
pubmed: 23895803
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.
doi: 10.1056/NEJMoa1611925
pubmed: 28605608
Jardine MJ, Mahaffey KW, Neal B, Agarwal R, Bakris GL, Brenner BM, Bull S, Cannon CP, Charytan DM, de Zeeuw D, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):462–72.
doi: 10.1159/000484633
pubmed: 29253846
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306.
doi: 10.1056/NEJMoa1811744
pubmed: 30990260
Gregg LP, Navaneethan SD. Are all SGLT2 inhibitors created Equal? Clin J Am Soc Nephrol. 2021;16(9):1309–11.
doi: 10.2215/CJN.09720721
pubmed: 34497107
pmcid: 8729580
Tuttle KR, Brosius FC 3rd, Cavender MA, Fioretto P, Fowler KJ, Heerspink HJL, Manley T, McGuire DK, Molitch ME, Mottl AK, et al. SGLT2 Inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation. Diabetes. 2021;70(1):1–16.
doi: 10.2337/dbi20-0040
pubmed: 33106255
Sen T, Heerspink HJL. A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors. Cell Metab. 2021;33(4):732–9.
doi: 10.1016/j.cmet.2021.02.016
pubmed: 33691091
Heerspink HJL, Perco P, Mulder S, Leierer J, Hansen MK, Heinzel A, Mayer G. Canagliflozin reduces inflammation and fibrosis biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia. 2019;62(7):1154–66.
doi: 10.1007/s00125-019-4859-4
pubmed: 31001673
pmcid: 6560022
Kidokoro K, Cherney DZI, Bozovic A, Nagasu H, Satoh M, Kanda E, Sasaki T, Kashihara N. Evaluation of glomerular hemodynamic function by Empagliflozin in diabetic mice using in vivo imaging. Circulation. 2019;140(4):303–15.
doi: 10.1161/CIRCULATIONAHA.118.037418
pubmed: 30773020