Sevelamer in Proteinuric CKD (ANSWER)
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|ClinicalTrials.gov Identifier: NCT01968759|
Recruitment Status : Completed
First Posted : October 24, 2013
Last Update Posted : October 12, 2015
Progressive renal impairment in chronic kidney diseases (CKD) may cause inability to excrete phosphate load, thus leading to the typical abnormalities of the mineral metabolism, such as increased phosphate and reduced calcium levels, 1,25- dihydroxyvitamin D deficiency and secondary hyperparathyroidism (HPT). Treatment with vitamin D analogues and/or phosphate binders ameliorates these abnormalities that are also associated with accelerated renal disease progression and increased cardiovascular risk. However in a post-hoc analysis of 331 patients with proteinuric chronic nephropathies included in the Ramipril Efficacy In Nephropathy (REIN) trial, increasing serum phosphate levels at inclusion, even within the normal reference range, were associated with an incremental risk of progression to End Stage Renal Disease (ESRD). Moreover, increasing levels of serum phosphate were associated with a progressively decreasing protective effect of ramipril therapy against progression to ESRD, to the point that the benefit of Angiotensin-Converting-Enzyme (ACE) inhibition was almost fully lost among patients with serum phosphate levels exceeding 4.5 mg/dL. This finding provided convincing evidence that phosphate plays a direct pathogenic role in patients with progressive nephropathies and that excess phosphate exposure may limit or even blunt the renoprotective effect of ACE inhibitor therapy in this population.
Sevelamer carbonate is a newly approved phosphate binder for chronic kidney disease (CKD) patients not yet on maintenance dialysis. Treatment with Sevelamer, in addition to correct hyperphosphatemia, was also found to ameliorate abnormalities of the mineral metabolism associated with accelerated renal disease progression and increased cardiovascular risk. Moreover, Sevelamer therapy reduces proteinuria in an animal model of uremia, an effect that in the long term might translate into significant renoprotection. These findings suggest that serum phosphate might be a specific target for renoprotective therapy in CKD patients and provide the background for randomized clinical trials to formally test whether reducing phosphate exposure by phosphate binding agents may serve to optimize the renoprotective effect of RAS inhibition in this population. Thus, whether phosphate reduction by Sevelamer carbonate therapy may have a specific antiproteinuric effect in humans with chronic nephropathies and residual proteinuria despite optimized RAS inhibitor therapy is worth investigating.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Kidney Disease||Drug: Sevelamer Drug: Ramipril and Irbesartan||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||53 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective, Randomized, Multicenter, Open, Blinded Endpoint (PROBE), Clinical Trial to Assess the Renal and Humoral Effects of Sevelamer Carbonate in Patients With Chronic Kidney Disease and Residual Proteinuria Despite Best Available Treatment|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||October 2015|
|Actual Study Completion Date :||October 2015|
Active Comparator: Ramipril and Irbesartan
Best available therapy including dual RAS blockade with Ramipril and Irbesartan
Drug: Ramipril and Irbesartan
Two tablets of Sevelamer carbonate 800 mg will be orally administered three times per day during the meals for 3 months.
Drug: Ramipril and Irbesartan
- 24-h urinary protein excretion [ Time Frame: Changes from Baseline at 3,4,7 and 8 month. ]
- Office blood pressure [ Time Frame: At every visit, up to 8 months. ]
- Glomerular Filtration Rate [ Time Frame: Changes from baseline at 3,4 and 7 month. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01968759
|Clinical Research Center for Rare Diseases|
|Ranica, Bergamo, Italy, 24020|
|Azienda Ospedaliera "Bianchi-Melacrino-Morelli" c/o Ospedali Riuniti U.O. Nefrologia, Dialisi e Trapianto|
|Reggio Calabria, Italy|