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

This study has been completed.
Sponsor:
Information provided by:
Nabi Biopharmaceuticals
ClinicalTrials.gov Identifier:
NCT00211939
First received: September 13, 2005
Last updated: December 26, 2007
Last verified: December 2007
  Purpose

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 Intervention Phase
Calcinosis
Arteriosclerosis
Hyperparathyroidism, Secondary
Drug: calcium acetate
Drug: sevelamer
Drug: atorvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CARE-2 (Calcium Acetate (PhosLo®)/Sevelamer(Renagel®) Evaluation Study 2)

Resource links provided by NLM:


Further study details as provided by Nabi Biopharmaceuticals:

Primary Outcome Measures:
  • electron-beam CT coronary artery calcification AGATSTON score [ Time Frame: change at 12 mo from baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • serum phosphorus [ Time Frame: Days 30-365 ] [ Designated as safety issue: No ]
  • calcium x phosphorus product [ Time Frame: Days 30-365 ] [ Designated as safety issue: No ]

Enrollment: 203
Study Start Date: January 2005
Study Completion Date: March 2007
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00211939

Locations
United States, Texas
University of Texas Health Sciences Center
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
Nabi Biopharmaceuticals
Investigators
Study Chair: Wajeh Y Qunibi, M.D. The University of Texas Health Science Center at San Antonio
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Paul Kessler, MD, Sr. VP, Clinical, Medical & Regulatory Affairs, Nabi Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT00211939     History of Changes
Other Study ID Numbers: Nabi 6404
Study First Received: September 13, 2005
Last Updated: December 26, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Nabi Biopharmaceuticals:
PhosLo (Calcium acetate)
Renagel (sevelamer, polyallylamine HCL)
kidney dialysis
hyperphosphatemia
Kidney failure

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Calcinosis
Hyperparathyroidism
Hyperparathyroidism, Secondary
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Parathyroid Diseases
Endocrine System Diseases
Calcium, Dietary
Atorvastatin
Sevelamer
Calcium acetate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Chelating Agents
Sequestering Agents

ClinicalTrials.gov processed this record on September 11, 2014