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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020872-49 | EudraCT Number |
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| Name | Class |
|---|---|
| Genzyme, a Sanofi Company | INDUSTRY |
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The purpose of this study is to evaluate in Chronic Kidney Disease (CKD) patients not on dialysis and who have an Fibroblast growth factor 23 (FGF23) serum levels elevated, the effect of non calcic phosphate binder: sevelamer carbonate. This treatment could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate. In addition, the investigators will describe the impact of the FGF23 level monitoring on the main phosphocalcium metabolism markers as phosphatemia, intact parathyroid hormone (iPTH), serum calcitriol and phosphaturia.
The total length of the study is 14 weeks divided in 2 parts the first part is the screening period she will stay 1 to 2 weeks and the second period with the treatment with permanent dosage during 12 weeks.
During the screening visit (Vo) inclusion and non inclusion criteria will be checked and the patient consent will be collected. Biological analysis will be performed.
If the patient still eligible after the reception of biological results, he will be randomized and will received, either sevelamer carbonate, either placebo. The study treatment will be begun at the randomisation visit (V1) the dosage will be 2 tablets 3 times per day (corresponding to 4.8g/d sevelamer carbonate for patient taken active medication).
Patient will be seen every 2 weeks after the first visit (+/-5days) during 6 weeks (visit2/day15, visit3/day30, visit4/day45) and 12 weeks after the randomisation visit (visit5/day90). This visits will include biological analysis, compliance evaluation, adverse events report, concomitant treatments reports.
After the consent signature, all the adverse events will be collected until the end of the study for the patient (Visit5 or end of the study visit). Serious adverse events will be collected until 30 days after the date of the end of the study.
The same dosage of the study treatment will be followed during all the study period except if the phosphatemia (evaluated during one analysis) is found above the normal range planned by the protocol. In this case, the dosage adaptations will be :
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | DOuble blinded, same labels than the active drug same dosage (2 tablets 3 times per day) during the meal |
|
| Sevelamer carbonate | Experimental | DOuble blinded, dosage 2 tablets 3 times per day corresponding to 4.8/d to taken during meals |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | dosage : 2 tablets 3 times per day corresponding taken during meals during 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Measurement of the serum levels of C terminal segment of fibroblast growth factor 23 (FGF23) and evaluation of sevelamer carbonate effect on this levels in comparison with placebo | Indeed the sevelamer carbonate could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate. | 12 weeks after the beginning of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of sevelamer carbonate effect on the serum levels of iPTH | 12 weeks after the beginning of treatment | |
| Evaluation of sevelamer carbonate effect on the serum levels of calcitriol (1 25(OH)2D3) | 12 weeks after the beginning of treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gabriel Choukroun, Ph D, M D | Centre Hospitalier Universitaire, Amiens | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Amiens service de nephrologie | Amiens | 8000 | France | |||
| CHU de Bordeaux Service de néphrologie |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17517792 | Background | Voormolen N, Noordzij M, Grootendorst DC, Beetz I, Sijpkens YW, van Manen JG, Boeschoten EW, Huisman RM, Krediet RT, Dekker FW; PREPARE study group. High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant. 2007 Oct;22(10):2909-16. doi: 10.1093/ndt/gfm286. Epub 2007 May 21. | |
| 18805347 |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D000069603 | Sevelamer |
| ID | Term |
|---|---|
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Sevelamer carbonate | Drug | dosage : 2 tablets 3 times per day corresponding taken during meals during 12 weeks ( each tablet :800mg sevelamer carbonate |
|
|
| Evaluation of sevelamer carbonate effect on the serum levels of others mineral metabolism parameters (phosphore, calcium, intact FGF-23 , 25(OH)D3, bone specific alkaline phosphatases, osteocalcin, collagen crosslink, C reactive protein) | 12 weeks after the beginning of treatment |
| Evaluation of sevelamer carbonate effect on the urinary levels of phosphate | 12 weeks after the beginning of treatment |
| Evaluation of sevelamer carbonate effect on the urinary levels of calcium | 12 weeks after the beginning of treatment |
| Evaluation of sevelamer carbonate effect on the urinary levels of creatinine | 12 weeks after the beginning of treatment |
| Evaluation of sevelamer carbonate effect on the urinary levels of urea | 12 weeks after the beginning of treatment |
| Evaluation of sevelamer carbonate effect on the serum and urinary levels of specific biomarkers (serum : fetuin A, para-cresyl sulfate, osteopontin) | 12 weeks after the beginning of treatment |
| Bordeaux |
| 33076 |
| France |
| CHU Caen service de néphrologie | Caen | 14033 | France |
| CHU Lyon service de néphrologie | Lyon | 69437 | France |
| CHU Marseille Service de néphrologie | Marseille | 13385 | France |
| CHU de Montpellier Hôpital Lapeyronie Service de Néphrologie | Montpellier | 34295 | France |
| CHU de Nice Service de néphrologie | Nice | 06002 | France |
| HĂ´pital Tenon Service de Nephrologie | Paris | 75020 | France |
| Hôpital Européen Georges Pompidou Service de Nephrologie | Paris | 75098 | France |
| CHU Reims service de néphrologie | Reims | 51092 | France |
| CHU St Etienne Hopital Nord Service de néphrologie | Saint-Etienne | 42055 | France |
| Clinique du Landy Centre de dialyse | Saint-Ouen | 93400 | France |
| Néphrologie - Dialyse Centre de Rein Artificiel | Tassin-la-Demi-Lune | 69160 | France |
| CH Valenciennes hémodialyse | Valenciennes | 59322 | France |
| CHU de Nancy service de néphrologie | Vandeuvre Les Nancy | 54511 | France |
| Levin A, Djurdjev O, Beaulieu M, Er L. Variability and risk factors for kidney disease progression and death following attainment of stage 4 CKD in a referred cohort. Am J Kidney Dis. 2008 Oct;52(4):661-71. doi: 10.1053/j.ajkd.2008.06.023. |
| 15615819 | Background | Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):520-8. doi: 10.1681/ASN.2004070602. Epub 2004 Dec 22. |
| 18359409 | Background | Vassalotti JA, Uribarri J, Chen SC, Li S, Wang C, Collins AJ, Calvo MS, Whaley-Connell AT, McCullough PA, Norris KC; Kidney Early Evaluation Program Investigators. Trends in mineral metabolism: Kidney Early Evaluation Program (KEEP) and the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Am J Kidney Dis. 2008 Apr;51(4 Suppl 2):S56-68. doi: 10.1053/j.ajkd.2007.12.018. |
| 18469306 | Background | Danziger J. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Nephrol Dial Transplant. 2008 Sep;23(9):2733-7. doi: 10.1093/ndt/gfn260. Epub 2008 May 9. No abstract available. |
| 16896512 | Background | Inaba M, Okuno S, Imanishi Y, Yamada S, Shioi A, Yamakawa T, Ishimura E, Nishizawa Y. Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients. Osteoporos Int. 2006 Oct;17(10):1506-13. doi: 10.1007/s00198-006-0154-6. Epub 2006 Aug 5. |
| 17656479 | Background | Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F; MMKD Study Group; Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007 Sep;18(9):2600-8. doi: 10.1681/ASN.2006080936. Epub 2007 Jul 26. |
| 18687639 | Background | Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008 Aug 7;359(6):584-92. doi: 10.1056/NEJMoa0706130. |
| 19395730 | Background | Jean G, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C. High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant. 2009 Sep;24(9):2792-6. doi: 10.1093/ndt/gfp191. Epub 2009 Apr 25. |
| 19797911 | Background | Peiskerova M, Kalousova M, Kratochvilova M, Dusilova-Sulkova S, Uhrova J, Bandur S, Malbohan IM, Zima T, Tesar V. Fibroblast growth factor 23 and matrix-metalloproteinases in patients with chronic kidney disease: are they associated with cardiovascular disease? Kidney Blood Press Res. 2009;32(4):276-83. doi: 10.1159/000243050. Epub 2009 Oct 1. |
| Background | JP Cristol, AS Bargnoux, AM Dupuy, M Morena, A Avignon and B Canaud. Biological markers of vascular calcifications in uremia. Médecine Nucléaire 2009; 33, 53-61. |
| 19534362 | Background | Stubbs JR, Quarles LD. Fibroblast growth factor 23: uremic toxin or innocent bystander in chronic kidney disease? Nephrol News Issues. 2009 May;23(6):33-4, 36-7. |
| 17567652 | Background | Westerberg PA, Linde T, Wikstrom B, Ljunggren O, Stridsberg M, Larsson TE. Regulation of fibroblast growth factor-23 in chronic kidney disease. Nephrol Dial Transplant. 2007 Nov;22(11):3202-7. doi: 10.1093/ndt/gfm347. Epub 2007 Jun 13. |
| 15264182 | Background | Shigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F, Fukagawa M. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004 Aug;44(2):250-6. doi: 10.1053/j.ajkd.2004.04.029. |
| 19631779 | Background | Tanaka H, Hamano T, Fujii N, Tomida K, Matsui I, Mikami S, Nagasawa Y, Ito T, Moriyama T, Horio M, Imai E, Isaka Y, Rakugi H. The impact of diabetes mellitus on vitamin D metabolism in predialysis patients. Bone. 2009 Nov;45(5):949-55. doi: 10.1016/j.bone.2009.07.016. Epub 2009 Jul 23. |
| 17943081 | Background | Urena Torres P, Friedlander G, de Vernejoul MC, Silve C, Prie D. Bone mass does not correlate with the serum fibroblast growth factor 23 in hemodialysis patients. Kidney Int. 2008 Jan;73(1):102-7. doi: 10.1038/sj.ki.5002622. Epub 2007 Oct 17. |
| 16395276 | Background | Nagano N, Miyata S, Abe M, Kobayashi N, Wakita S, Yamashita T, Wada M. Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Kidney Int. 2006 Feb;69(3):531-7. doi: 10.1038/sj.ki.5000020. |
| 19965540 | Background | Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moyses RM. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010 Feb;5(2):286-91. doi: 10.2215/CJN.05420709. Epub 2009 Nov 12. |
| 19644521 | Background | Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188. |
| 11904577 | Background | National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available. |
| 16908915 | Background | Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. doi: 10.7326/0003-4819-145-4-200608150-00004. |
| 29074818 | Result | Liabeuf S, Ryckelynck JP, El Esper N, Urena P, Combe C, Dussol B, Fouque D, Vanhille P, Frimat L, Thervet E, Mentaverri R, Prie D, Choukroun G; FRENCH Study collaborators. Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast Growth Factor 23 in CKD. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):1930-1940. doi: 10.2215/CJN.03030317. Epub 2017 Oct 26. |
| 40576086 | Derived | Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4. |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |