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Sevelamer in Proteinuric CKD (ANSWER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01968759
Recruitment Status : Completed
First Posted : October 24, 2013
Last Update Posted : October 12, 2015
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Active Comparator: Ramipril and Irbesartan
Best available therapy including dual RAS blockade with Ramipril and Irbesartan
Drug: Sevelamer
Drug: Ramipril and Irbesartan
Experimental: Sevelamer
Two tablets of Sevelamer carbonate 800 mg will be orally administered three times per day during the meals for 3 months.
Drug: Sevelamer
Drug: Ramipril and Irbesartan

Primary Outcome Measures :
  1. 24-h urinary protein excretion [ Time Frame: Changes from Baseline at 3,4,7 and 8 month. ]

Secondary Outcome Measures :
  1. Office blood pressure [ Time Frame: At every visit, up to 8 months. ]
  2. Glomerular Filtration Rate [ Time Frame: Changes from baseline at 3,4 and 7 month. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • age > 18 years;
  • estimated glomerular filtration rate (GFR) by simplified MDRD formula > 15 mL/min/1.73m2;
  • 24-h urinary protein excretion rate ≥ 0.5 g/24hour;
  • no concomitant treatment with phosphate binders;
  • written informed consent

Exclusion Criteria:

  • serum phosphate level < 2.5 or > 5.5 mg/dL;
  • patients with serum PTH levels >250 pg/mL without stable vitamin D (calcitriol or paricalcitol) or calcimimetics therapy from at least three months;
  • serum calcium level < 7.5 or >10.5 mg/dL;
  • history of congestive heart failure, myocardial infarction, cerebrovascular accident within the last 6 months;
  • cancer and any severe systemic disease or clinical condition that may jeopardize data interpretation or completion of the study;
  • presence of, or predisposition to, intestinal or ileus obstruction or severe gastrointestinal motility disorder (like severe constipation);
  • previous major gastrointestinal surgery;
  • previous kidney transplantation;
  • previous parathyroidectomy;
  • concomitant treatment with antiacid and phosphate binders with aluminium, magnesium, calcium or lanthanum;
  • pregnancy or breastfeeding;
  • childbearing potential without reliable contraceptive methods during the whole study period;
  • participation in any clinical trial using an investigational product or device during the 30 days preceding the first protocol visit;
  • alcohol or drug (excluding tobacco) abuse ;
  • inability to comply with the study procedures during the whole study period, legal incapacity.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01968759

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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
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Mario Negri Institute for Pharmacological Research Identifier: NCT01968759    
Other Study ID Numbers: ANSWER
2012-005416-26 ( EudraCT Number )
First Posted: October 24, 2013    Key Record Dates
Last Update Posted: October 12, 2015
Last Verified: October 2015
Keywords provided by Mario Negri Institute for Pharmacological Research:
Chronic kidney disease
Sevelamer carbonate
Phosphate binders
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Renal Insufficiency
Chronic Disease
Disease Attributes
Pathologic Processes
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Chelating Agents
Sequestering Agents