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CARE-2 (Calcium Acetate [PhosLo®]/Sevelamer[Renagel®] Evaluation Study 2) for Heart Calcification in Dialysis Patients

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: NCT00211939
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : January 8, 2008
Information provided by:
Nabi Biopharmaceuticals

Brief 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 valve.

Condition or disease Intervention/treatment Phase
Calcinosis Arteriosclerosis Hyperparathyroidism, Secondary Drug: calcium acetate Drug: sevelamer Drug: atorvastatin Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 203 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CARE-2 (Calcium Acetate (PhosLo®)/Sevelamer(Renagel®) Evaluation Study 2)
Study Start Date : January 2005
Actual Primary Completion Date : December 2006
Actual Study Completion Date : March 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Calcium

Arm Intervention/treatment
Experimental: 1
PhosLo + atorvastatin
Drug: calcium acetate
667 mg gelcap, 2-4 t.i.d titrated to serum phosphorus level
Other Name: PhosLo

Drug: atorvastatin
20 mg PO qD (in PhosLo group), or held until D60 (sevelamer group); titrate by LDL levels and liver function tests
Other Name: Lipitor

Active Comparator: 2
Sevelamer + atorvastatin
Drug: sevelamer
1-3 tablets t.i.d, titrated to serum phosphorus level
Other Name: Renagel

Drug: atorvastatin
20 mg PO qD (in PhosLo group), or held until D60 (sevelamer group); titrate by LDL levels and liver function tests
Other Name: Lipitor

Primary Outcome Measures :
  1. electron-beam CT coronary artery calcification AGATSTON score [ Time Frame: change at 12 mo from baseline ]

Secondary Outcome Measures :
  1. serum phosphorus [ Time Frame: Days 30-365 ]
  2. calcium x phosphorus product [ Time Frame: Days 30-365 ]

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:

  • 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

Exclusion Criteria:

  • Unstable angina pectoris
  • Severe congestive heart failure
  • Severe obstructive pulmonary disease requiring supplemental oxygen
  • Severe liver dysfunction
  • Severe malnutrition
  • Severe hyperparathyroidism
  • 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

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): NCT00211939

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United States, Texas
University of Texas Health Sciences Center
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
Nabi Biopharmaceuticals
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Study Chair: Wajeh Y Qunibi, M.D. The University of Texas Health Science Center at San Antonio
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Paul Kessler, MD, Sr. VP, Clinical, Medical & Regulatory Affairs, Nabi Biopharmaceuticals Identifier: NCT00211939    
Other Study ID Numbers: Nabi 6404
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: January 8, 2008
Last Verified: December 2007
Keywords provided by Nabi Biopharmaceuticals:
PhosLo (Calcium acetate)
Renagel (sevelamer, polyallylamine HCL)
kidney dialysis
Kidney failure
Additional relevant MeSH terms:
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Hyperparathyroidism, Secondary
Parathyroid Diseases
Endocrine System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Calcium acetate
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Chelating Agents
Sequestering Agents