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CompletedNCT00379899Updated Jul 23, 2014Results posted

ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

A Phase 4 interventional study of cinacalcet in Chronic Kidney Disease, End Stage Renal Disease and Coronary Artery Calcification, sponsored by Amgen. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-07-23.

Sponsored by Amgen · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
360
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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

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Conditions studied

  • Chronic Kidney Disease
  • End Stage Renal Disease
  • Coronary Artery Calcification
  • Vascular Calcification
  • Calcification
  • Cardiovascular Disease
  • Chronic Renal Failure
  • Hyperparathyroidism
  • Kidney Disease
  • Nephrology
  • Secondary Hyperparathyroidism

Keywords

  • calcification
  • vascular calcification
  • coronary vascular calcification
  • chronic kidney disease
  • end stage renal disease
  • dialysis
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In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 360 is above the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
360 participants (actual)

Study arms

  • Active comparator
    Control

    Standard of care, without use of cinacalcet.

    Drug: cinacalcet

Interventions

  • Drugcinacalcet

    Low dose vitamin D with cinacalcet

    Also known as: cinacalcet + low dose vitamin D

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. Absolute Change in PTH

    Absolute change from baseline in intact Parathyroid Hormone (iPTH)

    Time frame: Baseline and Week 52

  3. 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

  4. 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

  5. Percent Change in PTH

    Percent change from baseline in intact Parathyroid Hormone (iPTH)

    Time frame: Baseline and Week 52

  6. Absolute Change in Calcium

    Absolute change from baseline in serum calcium to weeks 44 through 52

    Time frame: Baseline and Weeks 44 through 52

  7. 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

  8. Absolute Change in Phosphorus

    Absolute change from baseline in serum phosphorus to weeks 44 through 52

    Time frame: Baseline and Weeks 44 through 52

  9. Percent Change in Phosphorus

    Percent change from baseline in serum phosphorus to weeks 44 through 52

    Time frame: Baseline and Weeks 44 through 52

  10. 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

  11. 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

07

Results

Posted Oct 27, 2010

Participant flow

Participants were enrolled from 27 October 2006 through 2 May 2008

Participant flow — Overall Study
MilestoneCinacalcetControl
Started180180
Completed140140
Not completed4040
Withdrew: Adverse event73
Withdrew: Death1010
Withdrew: Lost to follow-up24
Withdrew: Physician decision34
Withdrew: Withdrawal by subject55
Withdrew: Ineligibility determined01
Withdrew: Noncompliance11
Withdrew: Parathyroidectomy02
Withdrew: Renal transplantation54
Withdrew: Coronary artery bypass graft11
Withdrew: Other protocol-specified criteria34
Withdrew: Other31

Outcome measures

PrimaryPercent 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
Reported as:
Mean · Units on a scale
Percent Change From Baseline in CAC Score
Units on a scaleCinacalcetControl
Percent Change From Baseline in CAC Score43.74 ± 7.4057.39 ± 7.77
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.073Adjusted for screening total coronary artery calcification score stratification factor (≥ 30 to 399, ≥ 400 to 999, and ≥ 1000)
SecondaryNumber 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
Reported as:
Number · Participants
Number of Participants Achieving > 15% Progression of CAC.
ParticipantsCinacalcetControl
Number of Participants Achieving > 15% Progression of CAC.6377
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.094 · Odds ratio (or): 0.62 · 95% CI 0.36 to 1.08Logit estimates (Cinacalcet:Control)
SecondaryAbsolute Change in PTH

Absolute change from baseline in intact Parathyroid Hormone (iPTH)

Time frame:
Baseline and Week 52
Reported as:
Mean · pg/mL
Absolute Change in PTH
pg/mLCinacalcetControl
Absolute Change in PTH-132.86 ± 29.46-71.55 ± 30.83
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.018Adjusted for screening total coronary artery calcification score stratification factor
SecondaryChange 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
Reported as:
Mean · Units on a scale
Change From Baseline in AC Score
Units on a scaleCinacalcetControl
Change From Baseline in AC Score935.92 ± 233.811677.28 ± 385.39
SecondaryChange 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
Reported as:
Mean · Units on a scale
Change From Baseline of the Progression of AVC.
Units on a scaleCinacalcetControl
Change From Baseline of the Progression of AVC.24.29 ± 24.1955.96 ± 18.34
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.258
SecondaryPercent Change in PTH

Percent change from baseline in intact Parathyroid Hormone (iPTH)

Time frame:
Baseline and Week 52
Reported as:
Mean · Percentage
Percent Change in PTH
PercentageCinacalcetControl
Percent Change in PTH-18.18 ± 5.53-3.88 ± 5.70
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.011Adjusted for screening total coronary artery calcification score stratification factor
SecondaryAbsolute Change in Calcium

Absolute change from baseline in serum calcium to weeks 44 through 52

Time frame:
Baseline and Weeks 44 through 52
Reported as:
Mean · mg/dL
Absolute Change in Calcium
mg/dLCinacalcetControl
Absolute Change in Calcium-0.51 ± 0.070.17 ± 0.05
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = <0.001Adjusted for screening total coronary artery calcification score stratification factor
SecondaryPercent Change in Calcium

Percent change from baseline in corrected serum calcium to weeks 44 through 52

Time frame:
Baseline and Weeks 44 through 52
Reported as:
Mean · Percentage
Percent Change in Calcium
PercentageCinacalcetControl
Percent Change in Calcium-5.24 ± 0.721.98 ± 0.59
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = <0.001Adjusted for screening total coronary artery calcification score stratification factor
SecondaryAbsolute Change in Phosphorus

Absolute change from baseline in serum phosphorus to weeks 44 through 52

Time frame:
Baseline and Weeks 44 through 52
Reported as:
Mean · mg/dL
Absolute Change in Phosphorus
mg/dLCinacalcetControl
Absolute Change in Phosphorus-0.92 ± 0.18-0.24 ± 0.16
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.025Adjusted for screening total coronary artery calcification score stratification factor
SecondaryPercent Change in Phosphorus

Percent change from baseline in serum phosphorus to weeks 44 through 52

Time frame:
Baseline and Weeks 44 through 52
Reported as:
Mean · Percentage
Percent Change in Phosphorus
PercentageCinacalcetControl
Percent Change in Phosphorus-9.63 ± 2.935.26 ± 5.48
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = 0.021Adjusted for screening total coronary artery calcification score stratification factor
SecondaryAbsolute 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
Reported as:
Mean · (mg/dL)2
Absolute Change in Ca x P
(mg/dL)2CinacalcetControl
Absolute Change in Ca x P-11.22 ± 1.68-1.32 ± 1.44
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = <0.001Adjusted for screening total coronary artery calcification score stratification factor
SecondaryPercent 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
Reported as:
Mean · Percentage
Percent Change in Ca x P
PercentageCinacalcetControl
Percent Change in Ca x P-14.56 ± 2.886.54 ± 5.15
Statistical analysis
  • Cinacalcet vs Control · Cochran-Mantel-Haenszel · p = <0.001Adjusted for screening total coronary artery calcification score stratification factor

Adverse events

Collected over 52 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cinacalcet—88/180 (48.9%)95/180 (52.8%)
Control Group—82/180 (45.6%)93/180 (51.7%)
Most frequent serious events
Showing 10 of 247
Most frequent serious events
EventCinacalcetControl Group
AnaemiaBlood and lymphatic system disorders7/1803/180
Angina pectorisCardiac disorders7/1804/180
PneumoniaInfections and infestations3/1807/180
Cardiac failure congestiveCardiac disorders6/1802/180
Arteriovenous fistula thrombosisInjury, poisoning and procedural complications6/1803/180
HyperkalaemiaMetabolism and nutrition disorders6/1803/180
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders6/1802/180
HypertensionVascular disorders4/1806/180
PyrexiaGeneral disorders5/1804/180
SepsisInfections and infestations5/1804/180
Most frequent other events
Showing 10 of 19
Most frequent other events
EventCinacalcetControl Group
DiarrhoeaGastrointestinal disorders29/18022/180
NauseaGastrointestinal disorders29/18014/180
VomitingGastrointestinal disorders23/18022/180
CoughRespiratory, thoracic and mediastinal disorders18/18023/180
Pain in extremityMusculoskeletal and connective tissue disorders7/18022/180
HeadacheNervous system disorders13/18021/180
DyspnoeaRespiratory, thoracic and mediastinal disorders9/18017/180
ArthralgiaMusculoskeletal and connective tissue disorders5/18016/180
HypocalcaemiaMetabolism and nutrition disorders14/1801/180
HypertensionVascular disorders14/1805/180

Baseline characteristics

Age, Continuous
Age, Continuous(Years)CinacalcetControlTotal
Mean61.2 ± 12.661.8 ± 12.861.5 ± 12.7
Sex: Female, Male
Sex: Female, Male(Participants)CinacalcetControlTotal
Female6885153
Male11295207
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)CinacalcetControlTotal
American Indian or Alaska Native101
Asian4610
Black or African American454085
Hispanic or Latino111425
Native Hawaiian or Other Pacific Islander202
White or Caucasian116120236
Other101
Coronary Artery Calcification Score Stratification Factor
Coronary Artery Calcification Score Stratification Factor(Participants)CinacalcetControlTotal
≥30 to 3996767134
≥400 to 999474794
≥10006666132
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Bellasi A, Reiner M, Petavy F, Goodman W, Floege J, Raggi P. Presence of valvular calcification predicts the response to cinacalcet: data from the ADVANCE study. J Heart Valve Dis. 2013 May;22(3):391-9. PubMed 24151766 ↗
  • Boer R, Lalla AM, Belozeroff V. Cost-effectiveness of cinacalcet in secondary hyperparathyroidism in the United States. J Med Econ. 2012;15(3):509-20. doi: 10.3111/13696998.2012.664799. Epub 2012 Feb 21. PubMed 22313328 ↗
  • Floege J, Raggi P, Block GA, Torres PU, Csiky B, Naso A, Nossuli K, Moustafa M, Goodman WG, Lopez N, Downey G, Dehmel B, Chertow GM; ADVANCE Study group. Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2010 Jun;25(6):1916-23. doi: 10.1093/ndt/gfp762. Epub 2010 Jan 27. PubMed 20110249 ↗
  • Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K, Moustafa M, Goodman WG, Lopez N, Downey G, Dehmel B, Floege J; ADVANCE Study Group. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011 Apr;26(4):1327-39. doi: 10.1093/ndt/gfq725. Epub 2010 Dec 8. PubMed 21148030 ↗
  • Urena-Torres PA, Floege J, Hawley CM, Pedagogos E, Goodman WG, Petavy F, Reiner M, Raggi P. Protocol adherence and the progression of cardiovascular calcification in the ADVANCE study. Nephrol Dial Transplant. 2013 Jan;28(1):146-52. doi: 10.1093/ndt/gfs356. Epub 2012 Sep 30. PubMed 23028103 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 23, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00379899
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Sep 25, 2006
Start date
Sep 2006
Primary completion
May 2009
Completion
Nov 2009
Results posted
Oct 27, 2010
Last update
Jul 23, 2014

Study contacts

MD
study director · Amgen
View the source record on ClinicalTrials.gov ↗

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