CalcinosisPhase 4NCT00211939
CARE-2 (Calcium Acetate [PhosLo®]/Sevelamer[Renagel®] Evaluation Study 2) for Heart Calcification in Dialysis Patients
A Phase 4 study testing calcium acetate, sevelamer and atorvastatin in people with Calcinosis and Arteriosclerosis, run by Nabi Biopharmaceuticals at 1 site in United States.
Trial summary
The purpose of the study is to evaluate the effects of two phosphate binders, PhosLo and sevelamer, on heart calcification in dialysis patients. The study will use a non-invasive technique, electron beam computed tomography (CT) scanning, to measure calcium in the coronary arteries, the aortic valve, and the mitral… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Calcinosis, Arteriosclerosis, Hyperparathyroidism, Secondary
- What is being tested?
- calcium acetate, sevelamer and atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 203 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Mar 2007
- Phase
- Phase 4
- 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
- Eligible subjects will be male or female patients with end-stage renal disease on maintenance hemodialysis for less than 5 years, with elevated LDL cholesterol
- Currently treated with oral phosphate binders
- Coronary artery calcium scores of 30 to 5000 Agatston units measured by electron beam CT scanning
- Written informed consent
- Negative serum pregnancy test if appropriate
- Expect to comply with protocol procedures and schedule
Who cannot join
- Unstable angina pectoris
- Severe congestive heart failure
- Severe obstructive pulmonary disease requiring supplemental oxygen
- Severe liver dysfunction
- Severe malnutrition
- Severe hyperparathyroidism
Show all 15Show fewer
- Known HIV
- Active malignancy for which the subject is receiving chemotherapy or radiation
- Planned renal transplant within the next year
- Clinical evidence of calciphylaxis or recent history of hypercalcemia
- History of obstructed bowels
- Hypersensitivity to any of the components of the study medication
- History of swallowing disorders
- Weight > 300 pounds
- Any condition which makes patient participation not in the patient's best interest
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Sciences Center
San Antonio, Texas, 78229-3900
About this study
Official title: CARE-2 (Calcium Acetate (PhosLo®)/Sevelamer(Renagel®) Evaluation Study 2)
The purpose of the study is to evaluate the effects of two phosphate binders, PhosLo and sevelamer, on heart calcification in dialysis patients. The study will use a non-invasive technique, electron beam computed tomography (CT) scanning, to measure calcium in the coronary arteries, the aortic valve, and the mitral valve.
Read the detailed description
Cardiovascular disease is the major cause of death and disability in patients with end-stage renal disease on hemodialysis. It has been hypothesized that ingestion of calcium-based phosphate binders results in net positive calcium balance and vascular calcium deposition. Chertow et al. tested the role of ingested calcium in the progression of cardiovascular calcification in the Treat-To-Goal study (Kidney International 62:245, 2002). They reported that patients treated with calcium-based phosphate binders demonstrated progressive cardiovascular calcification, while patients treated with a calcium-free binder, sevelamer, showed stabilization or improvement in calcification scores. However, the protocol did not prohibit intake of supplemental oral calcium in the sevelamer group, which confounded their ability to accurately test the calcium hypothesis. Moreover, due to the cholesterol sequestering activities of sevelamer, the low-density lipoprotein (LDL) cholesterol was lower among sevelamer-treated patients than the calcium treated patients, resulting in a major imbalance in a cardiovascular risk factor. Lowering LDL level reduces progression of CVC and therefore confounds interpretation of the study. Subsequently, it has been reported in the lay press that patients randomized to sevelamer or calcium-based binders in the Dialysis Clinical Outcomes Revisited (DCOR) study have failed to show a difference in mortality or major secondary endpoints (Suki et al., To be presented American Society of Nephrology November 2005). To circumvent these limitations, the CARE-2 study will test the hypothesis that if LDL levels are lowered to a similar level in calcium acetate and sevelamer-treated patients, there will be no difference in the progression of cardiac calcification. CARE-2 will randomize patients with elevated LDL to calcium acetate or sevelamer. Atorvastatin is added to achieve LDL < 70 mg/dL in both treatment groups. The primary endpoint is change in cardiac calcification scores, determined by electron beam scanning after 1 year. Secondary endpoints include the ability of calcium acetate and sevelamer to control phosphorus and meet NKF-K/DOQI guidelines.
- Conditions
- Calcinosis, Arteriosclerosis, Hyperparathyroidism, Secondary
- Being tested
- calcium acetate, sevelamer, atorvastatin
- Keywords
- PhosLo (Calcium acetate), Renagel (sevelamer, polyallylamine HCL), kidney dialysis, hyperphosphatemia, Kidney failure
- Medical subject headings
- Calcinosis, Arteriosclerosis, Hyperparathyroidism, Secondary, Hyperphosphatemia, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
calcium acetateDrug
Also called PhosLo
667 mg gelcap, 2-4 t.i.d titrated to serum phosphorus level
sevelamerDrug
Also called Renagel
1-3 tablets t.i.d, titrated to serum phosphorus level
atorvastatinDrug
Also called Lipitor
20 mg PO qD (in PhosLo group), or held until D60 (sevelamer group); titrate by LDL levels and liver function tests
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | PhosLo + atorvastatin Receives: Drug: calcium acetate; Drug: atorvastatin |
| 2 | Active comparator | Sevelamer + atorvastatin Receives: Drug: sevelamer; Drug: atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
electron-beam CT coronary artery calcification AGATSTON score
Measured: change at 12 mo from baseline
Secondary outcomes (2)
serum phosphorus
Measured: Days 30-365
calcium x phosphorus product
Measured: Days 30-365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startJan 2005
- Primary completionDec 2006
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for CalcinosisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 203 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nabi Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Wajeh Y Qunibi, M.D., Study chair, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00211939
- Sponsor's protocol ID
- Nabi 6404
- Status last verified
- Dec 2007
- First submitted
- 13 Sep 2005
- Last updated
- 8 Jan 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Chertow GM, Burke SK, Raggi P; Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002 Jul;62(1):245-52. doi: 10.1046/j.1523-1755.2002.00434.x.
PubMed 12081584Natale 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 40576086Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD, Diaz-Buxo JA, Budoff M; CARE-2 Investigators. A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis. 2008 Jun;51(6):952-65. doi: 10.1053/j.ajkd.2008.02.298. Epub 2008 Apr 18.
PubMed 18423809
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CARE-2 (Calcium Acetate (PhosLo®)/Sevelamer(Renagel®) Evaluation Study 2)
- ClinicalTrials.gov ID
- NCT00211939
- Acronym / sponsor ID
- Nabi 6404
- Conditions
- Calcinosis, Arteriosclerosis, Hyperparathyroidism, Secondary
- Keywords
- PhosLo (Calcium acetate), Renagel (sevelamer, polyallylamine HCL), kidney dialysis, hyperphosphatemia, Kidney failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 203 participants (actual)
- Lead sponsor
- Nabi BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2005
- Primary completion
- Dec 2006 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 21 Sep 2005 (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.
The purpose of the study is to evaluate the effects of two phosphate binders, PhosLo and sevelamer, on heart calcification in dialysis patients. The study will use a non-invasive technique, electron beam computed tomography (CT) scanning, to measure calcium in the coronary arteries, the aortic valve, and the mitral valve.
Detailed description
Cardiovascular disease is the major cause of death and disability in patients with end-stage renal disease on hemodialysis. It has been hypothesized that ingestion of calcium-based phosphate binders results in net positive calcium balance and vascular calcium deposition. Chertow et al. tested the role of ingested calcium in the progression of cardiovascular calcification in the Treat-To-Goal study (Kidney International 62:245, 2002). They reported that patients treated with calcium-based phosphate binders demonstrated progressive cardiovascular calcification, while patients treated with a calcium-free binder, sevelamer, showed stabilization or improvement in calcification scores. However, the protocol did not prohibit intake of supplemental oral calcium in the sevelamer group, which confounded their ability to accurately test the calcium hypothesis. Moreover, due to the cholesterol sequestering activities of sevelamer, the low-density lipoprotein (LDL) cholesterol was lower among sevelamer-treated patients than the calcium treated patients, resulting in a major imbalance in a cardiovascular risk factor. Lowering LDL level reduces progression of CVC and therefore confounds interpretation of the study. Subsequently, it has been reported in the lay press that patients randomized to sevelamer or calcium-based binders in the Dialysis Clinical Outcomes Revisited (DCOR) study have failed to show a difference in mortality or major secondary endpoints (Suki et al., To be presented American Society of Nephrology November 2005). To circumvent these limitations, the CARE-2 study will test the hypothesis that if LDL levels are lowered to a similar level in calcium acetate and sevelamer-treated patients, there will be no difference in the progression of cardiac calcification. CARE-2 will randomize patients with elevated LDL to calcium acetate or sevelamer. Atorvastatin is added to achieve LDL < 70 mg/dL in both treatment groups. The primary endpoint is change in cardiac calcification scores, determined by electron beam scanning after 1 year. Secondary endpoints include the ability of calcium acetate and sevelamer to control phosphorus and meet NKF-K/DOQI guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: calcium acetate, Drug: atorvastatinPhosLo + atorvastatin |
| 2 | Active comparator | Drug: sevelamer, Drug: atorvastatinSevelamer + atorvastatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Eligible subjects will be male or female patients with end-stage renal disease on maintenance hemodialysis for less than 5 years, with elevated LDL cholesterol
- Currently treated with oral phosphate binders
- Coronary artery calcium scores of 30 to 5000 Agatston units measured by electron beam CT scanning
- Written informed consent
- Negative serum pregnancy test if appropriate
Key exclusion criteria (15 listed)
- Unstable angina pectoris
- Severe congestive heart failure
- Severe obstructive pulmonary disease requiring supplemental oxygen
- Severe liver dysfunction
- Severe malnutrition
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 |
|---|---|---|
| calcium acetateAlso: PhosLo667 mg gelcap, 2-4 t.i.d titrated to serum phosphorus level | Drug | 1 |
| sevelamerAlso: Renagel1-3 tablets t.i.d, titrated to serum phosphorus level | Drug | 2 |
| atorvastatinAlso: Lipitor20 mg PO qD (in PhosLo group), or held until D60 (sevelamer group); titrate by LDL levels and liver function tests | Drug | 1, 2 |
Primary outcome
electron-beam CT coronary artery calcification AGATSTON score
Time frame: change at 12 mo from baseline
2 secondary outcomes
serum phosphorus
Time frame: Days 30-365
calcium x phosphorus product
Time frame: Days 30-365
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 8 Jan 2008.
- Background: PubMed 12081584Chertow GM, Burke SK, Raggi P; Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002 Jul;62(1):245-52. doi: 10.1046/j.1523-1755.2002.00434.x.
- 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 18423809Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD, Diaz-Buxo JA, Budoff M; CARE-2 Investigators. A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis. 2008 Jun;51(6):952-65. doi: 10.1053/j.ajkd.2008.02.298. Epub 2008 Apr 18.
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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.
Wajeh Y Qunibi, M.D. study chair
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing calcium acetate, sevelamer and atorvastatin in people with Calcinosis and Arteriosclerosis, run by Nabi Biopharmaceuticals at 1 site in United States.
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 6 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 8 Jan 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
electron-beam CT coronary artery calcification AGATSTON score (time frame: change at 12 mo from baseline). 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 NCT00211939, which also lists 3 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 8 Jan 2008.