Calcification, Cardiovascular Disease, Chronic Kidney Disease, Chronic Renal Failure, Coronary Artery Calcification, End Stage Renal Disease, Hyperparathyroidism, Kidney Disease, Nephrology, Secondary Hyperparathyroidism, Vascular Calcification
Conditions
Keywords
calcification, vascular calcification, coronary vascular calcification, chronic kidney disease, end stage renal disease, dialysis
Brief summary
The purpose of this study is to evaluate whether cinacalcet + low dose vitamin D attenuates the progression of vascular calcification over one year, compared with a treatment regimen that includes flexible vitamin D dosing in the absence of cinacalcet, in subjects with chronic kidney disease receiving hemodialysis
Interventions
DRUGcinacalcet
Low dose vitamin D with cinacalcet
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults with chronic kidney disease receiving hemodialysis. * Lab tests required at screening include Parathyroid Hormone (PTH), calcium, and phosphorus. * A screening coronary artery calcification score of at least 30.
Exclusion criteria
* Subjects on non-calcium or aluminum containing phosphate binders (example: sevelamer HCl, lanthanum) 30 days prior to screening. * Subjects on cinacalcet 30 days prior to screening. * Current or previous use of some osteoporosis medications. * Started or required change in cholesterol lowering medications within 30 days before screening. * Abnormal rhythm of the heart. * Parathyroidectomy done within 3 months prior to screening. * Anticipated parathyroidectomy or kidney transplant. * Current intolerance to oral medications, or inability to swallow. * Unstable medical condition. * Currently enrolled, or fewer than 30 days have passed since subject used another investigational device or drug. * Pregnancy or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in CAC Score | Baseline and Week 52 | Percent Change from baseline to week 52 in coronary artery calcification (CAC) score. CAC score ranges from 0 to 7500, with 0 representing no calcification. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in PTH | Baseline and Week 52 | Absolute change from baseline in intact Parathyroid Hormone (iPTH) |
| Change From Baseline in AC Score | Baseline and Week 52 | Change from baseline in aortic calcification (AC) score at week 52. AC score ranges from 0 to \>75,000, with 0 representing no calcification. |
| Change From Baseline of the Progression of AVC. | Baseline and Week 52 | Change from baseline in the aortic valve calcification (AVC) score. AVC score ranges from 0 to \>10,000, with 0 representing no calcification. |
| Percent Change in PTH | Baseline and Week 52 | Percent change from baseline in intact Parathyroid Hormone (iPTH) |
| Absolute Change in Calcium | Baseline and Weeks 44 through 52 | Absolute change from baseline in serum calcium to weeks 44 through 52 |
| Number of Participants Achieving > 15% Progression of CAC. | 52 weeks | Number of participants achieving \>15% progression of coronary artery calcification (CAC) at week 52 |
| Absolute Change in Phosphorus | Baseline and Weeks 44 through 52 | Absolute change from baseline in serum phosphorus to weeks 44 through 52 |
| Percent Change in Phosphorus | Baseline and Weeks 44 through 52 | Percent change from baseline in serum phosphorus to weeks 44 through 52 |
| Absolute Change in Ca x P | Baseline and Weeks 44 through 52 | Absolute change from baseline in corrected serum calcium x phosphorus to week 44 through week 52 |
| Percent Change in Ca x P | Baseline and Weeks 44 through 52 | Percent change from baseline in corrected serum calcium x phosphorus (Ca x P) to weeks 44 through 52 |
| Percent Change in Calcium | Baseline and Weeks 44 through 52 | Percent change from baseline in corrected serum calcium to weeks 44 through 52 |
Participant flow
Recruitment details
Participants were enrolled from 27 October 2006 through 2 May 2008
Participants by arm
| Arm | Count |
|---|---|
| Cinacalcet Cinacalcet plus low dose vitamin D | 180 |
| Control Flexible vitamin D dosing | 180 |
| Total | 360 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 3 |
| Overall Study | Coronary artery bypass graft | 1 | 1 |
| Overall Study | Death | 10 | 10 |
| Overall Study | Ineligibility determined | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Noncompliance | 1 | 1 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Other protocol-specified criteria | 3 | 4 |
| Overall Study | Parathyroidectomy | 0 | 2 |
| Overall Study | Physician Decision | 3 | 4 |
| Overall Study | Renal transplantation | 5 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Cinacalcet | Control | Total |
|---|---|---|---|
| Age, Continuous | 61.2 Years STANDARD_DEVIATION 12.6 | 61.8 Years STANDARD_DEVIATION 12.8 | 61.5 Years STANDARD_DEVIATION 12.7 |
| Coronary Artery Calcification Score Stratification Factor ≥1000 | 66 Participants | 66 Participants | 132 Participants |
| Coronary Artery Calcification Score Stratification Factor ≥30 to 399 | 67 Participants | 67 Participants | 134 Participants |
| Coronary Artery Calcification Score Stratification Factor ≥400 to 999 | 47 Participants | 47 Participants | 94 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 45 Participants | 40 Participants | 85 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 11 Participants | 14 Participants | 25 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 116 Participants | 120 Participants | 236 Participants |
| Sex: Female, Male Female | 68 Participants | 85 Participants | 153 Participants |
| Sex: Female, Male Male | 112 Participants | 95 Participants | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 95 / 180 | 93 / 180 |
| serious Total, serious adverse events | 88 / 180 | 82 / 180 |
Outcome results
Primary
Percent Change From Baseline in CAC Score
Percent Change from baseline to week 52 in coronary artery calcification (CAC) score. CAC score ranges from 0 to 7500, with 0 representing no calcification.
Time frame: Baseline and Week 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in CAC Score | 43.74 Units on a scale | Standard Error 7.4 |
| Control | Percent Change From Baseline in CAC Score | 57.39 Units on a scale | Standard Error 7.77 |
p-value: 0.073Cochran-Mantel-Haenszel
Secondary
Absolute Change in Calcium
Absolute change from baseline in serum calcium to weeks 44 through 52
Time frame: Baseline and Weeks 44 through 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Absolute Change in Calcium | -0.51 mg/dL | Standard Error 0.07 |
| Control | Absolute Change in Calcium | 0.17 mg/dL | Standard Error 0.05 |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Absolute Change in Ca x P
Absolute change from baseline in corrected serum calcium x phosphorus to week 44 through week 52
Time frame: Baseline and Weeks 44 through 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Absolute Change in Ca x P | -11.22 (mg/dL)2 | Standard Error 1.68 |
| Control | Absolute Change in Ca x P | -1.32 (mg/dL)2 | Standard Error 1.44 |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Absolute Change in Phosphorus
Absolute change from baseline in serum phosphorus to weeks 44 through 52
Time frame: Baseline and Weeks 44 through 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Absolute Change in Phosphorus | -0.92 mg/dL | Standard Error 0.18 |
| Control | Absolute Change in Phosphorus | -0.24 mg/dL | Standard Error 0.16 |
p-value: 0.025Cochran-Mantel-Haenszel
Secondary
Absolute Change in PTH
Absolute change from baseline in intact Parathyroid Hormone (iPTH)
Time frame: Baseline and Week 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Absolute Change in PTH | -132.86 pg/mL | Standard Error 29.46 |
| Control | Absolute Change in PTH | -71.55 pg/mL | Standard Error 30.83 |
p-value: 0.018Cochran-Mantel-Haenszel
Secondary
Change From Baseline in AC Score
Change from baseline in aortic calcification (AC) score at week 52. AC score ranges from 0 to \>75,000, with 0 representing no calcification.
Time frame: Baseline and Week 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Change From Baseline in AC Score | 935.92 Units on a scale | Standard Error 233.81 |
| Control | Change From Baseline in AC Score | 1677.28 Units on a scale | Standard Error 385.39 |
Secondary
Change From Baseline of the Progression of AVC.
Change from baseline in the aortic valve calcification (AVC) score. AVC score ranges from 0 to \>10,000, with 0 representing no calcification.
Time frame: Baseline and Week 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Change From Baseline of the Progression of AVC. | 24.29 Units on a scale | Standard Error 24.19 |
| Control | Change From Baseline of the Progression of AVC. | 55.96 Units on a scale | Standard Error 18.34 |
p-value: 0.258Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving > 15% Progression of CAC.
Number of participants achieving \>15% progression of coronary artery calcification (CAC) at week 52
Time frame: 52 weeks
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cinacalcet | Number of Participants Achieving > 15% Progression of CAC. | 63 Participants |
| Control | Number of Participants Achieving > 15% Progression of CAC. | 77 Participants |
p-value: 0.09495% CI: [0.36, 1.08]Cochran-Mantel-Haenszel
Secondary
Percent Change in Calcium
Percent change from baseline in corrected serum calcium to weeks 44 through 52
Time frame: Baseline and Weeks 44 through 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change in Calcium | -5.24 Percentage | Standard Error 0.72 |
| Control | Percent Change in Calcium | 1.98 Percentage | Standard Error 0.59 |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percent Change in Ca x P
Percent change from baseline in corrected serum calcium x phosphorus (Ca x P) to weeks 44 through 52
Time frame: Baseline and Weeks 44 through 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change in Ca x P | -14.56 Percentage | Standard Error 2.88 |
| Control | Percent Change in Ca x P | 6.54 Percentage | Standard Error 5.15 |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percent Change in Phosphorus
Percent change from baseline in serum phosphorus to weeks 44 through 52
Time frame: Baseline and Weeks 44 through 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change in Phosphorus | -9.63 Percentage | Standard Error 2.93 |
| Control | Percent Change in Phosphorus | 5.26 Percentage | Standard Error 5.48 |
p-value: 0.021Cochran-Mantel-Haenszel
Secondary
Percent Change in PTH
Percent change from baseline in intact Parathyroid Hormone (iPTH)
Time frame: Baseline and Week 52
Population: Efficacy Evaluable Analysis Set, composed of all randomized participants with a baseline and a week 52 coronary artery calcification score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change in PTH | -18.18 Percentage | Standard Error 5.53 |
| Control | Percent Change in PTH | -3.88 Percentage | Standard Error 5.7 |
p-value: 0.011Cochran-Mantel-Haenszel