Chronic Kidney DiseasePhase 2ANSWERNCT01968759
Sevelamer in Proteinuric CKD
A Phase 2 study testing Sevelamer and Ramipril and Irbesartan in people with Chronic Kidney Disease, run by Mario Negri Institute for Pharmacological Research at 2 sites in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Sevelamer and Ramipril and Irbesartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 2 sitesItaly
- Study dates
- Oct 2013to Oct 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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);
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- 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.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Clinical Research Center for Rare Diseases
Ranica, Bergamo, 24020
Azienda Ospedaliera "Bianchi-Melacrino-Morelli" c/o Ospedali Riuniti U.O. Nefrologia, Dialisi e Trapianto
Reggio Calabria, Reggio Calabria
About this study
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
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.
- Conditions
- Chronic Kidney Disease
- Being tested
- Sevelamer, Ramipril and Irbesartan
- Keywords
- Chronic kidney disease, Sevelamer carbonate, Proteinuria, Phosphate binders
- Medical subject headings
- Renal Insufficiency, Chronic, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevelamerDrug
Ramipril and IrbesartanDrug
| Study group | Role | What they receive |
|---|---|---|
| Ramipril and Irbesartan | Active comparator | Best available therapy including dual RAS blockade with Ramipril and Irbesartan Receives: Drug: Sevelamer; Drug: Ramipril and Irbesartan |
| Sevelamer | Experimental | Two tablets of Sevelamer carbonate 800 mg will be orally administered three times per day during the meals for 3 months. Receives: Drug: Sevelamer; Drug: Ramipril and Irbesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-h urinary protein excretion
Measured: Changes from Baseline at 3,4,7 and 8 month.
Secondary outcomes (2)
Office blood pressure
Measured: At every visit, up to 8 months.
Glomerular Filtration Rate
Measured: Changes from baseline at 3,4 and 7 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968759
- Sponsor's protocol ID
- ANSWER
- Other IDs
- 2012-005416-26
- Acronym
- ANSWER
- Status last verified
- Oct 2015
- First submitted
- 15 Oct 2013
- Last updated
- 12 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 40576086Ruggiero B, Trillini M, Tartaglione L, Rotondi S, Perticucci E, Tripepi R, Aparicio C, Lecchi V, Perna A, Peraro F, Villa D, Ferrari S, Cannata A, Mazzaferro S, Mallamaci F, Zoccali C, Bellasi A, Cozzolino M, Remuzzi G, Ruggenenti P, Kohan DE; ANSWER Study Organization. Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial. Am J Kidney Dis. 2019 Sep;74(3):338-350. doi: 10.1053/j.ajkd.2019.01.029. Epub 2019 Apr 23.
PubMed 31027883
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01968759
- Acronym / sponsor ID
- ANSWER / ANSWER
- Conditions
- Chronic Kidney Disease
- Keywords
- Chronic kidney disease, Sevelamer carbonate, Proteinuria, Phosphate binders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 24 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ramipril and Irbesartan | Active comparator | Drug: Sevelamer, Drug: Ramipril and IrbesartanBest available therapy including dual RAS blockade with Ramipril and Irbesartan |
| Sevelamer | Experimental | Drug: Sevelamer, Drug: Ramipril and IrbesartanTwo tablets of Sevelamer carbonate 800 mg will be orally administered three times per day during the meals for 3 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sevelamer | Drug | Ramipril and Irbesartan, Sevelamer |
| Ramipril and Irbesartan | Drug | Ramipril and Irbesartan, Sevelamer |
Primary outcome
24-h urinary protein excretion
Time frame: Changes from Baseline at 3,4,7 and 8 month.
2 secondary outcomes
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2015.
- Derived from this study: PubMed 40576086Natale 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.
- Derived from this study: PubMed 31027883Ruggiero B, Trillini M, Tartaglione L, Rotondi S, Perticucci E, Tripepi R, Aparicio C, Lecchi V, Perna A, Peraro F, Villa D, Ferrari S, Cannata A, Mazzaferro S, Mallamaci F, Zoccali C, Bellasi A, Cozzolino M, Remuzzi G, Ruggenenti P, Kohan DE; ANSWER Study Organization. Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial. Am J Kidney Dis. 2019 Sep;74(3):338-350. doi: 10.1053/j.ajkd.2019.01.029. Epub 2019 Apr 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sevelamer and Ramipril and Irbesartan in people with Chronic Kidney Disease, run by Mario Negri Institute for Pharmacological Research at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-h urinary protein excretion (time frame: Changes from Baseline at 3,4,7 and 8 month.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01968759, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2015.