E.V.O.L.V.E. Trial™: EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events

NCT ID: NCT00345839

Last Updated: 2022-11-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3883 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-22

Study Completion Date

2012-04-10

Brief Summary

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The purpose of this study is to evaluate the effects of cinacalcet (cinacalcet HCl or Sensipar®/Mimpara®) on cardiovascular events and death in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (HPT) who are receiving dialysis.

Detailed Description

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Secondary HPT is common in people with CKD. Patients with secondary HPT often have high parathyroid hormone (PTH) levels and may develop large parathyroid glands in the neck. Patients with secondary HPT may have bone disease (osteodystrophy). This bone disease may cause bone pain, fractures, and poor formation of red blood cells. Other problems from secondary HPT may include increases in blood levels of calcium and phosphorus. These may cause calcium to deposit in body tissues. Calcium deposits can cause arthritis (joint pain and swelling), muscle inflammation, itching, gangrene (death of soft tissue), or heart and lung problems. New evidence suggests that secondary HPT is associated with cardiovascular disease and increased death risk. The purpose of this study is to evaluate the effects of cinacalcet (cinacalcet HCl or Sensipar®/Mimpara®) on cardiovascular events (having to do with the heart and its blood vessels) and death in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (HPT) who are receiving dialysis. These events include death from any reason, heart attack and episodes where the heart does not get enough oxygen, peripheral vascular disease (narrowing of vessels that carry blood to the legs, arms, stomach or kidneys), and heart failure (a condition that occurs when the heart is unable to pump enough blood to meet the need's of the body's tissues)

Conditions

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Secondary Hyperparathyroidism Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Cinacalcet

Group Type EXPERIMENTAL

Cinacalcet

Intervention Type DRUG

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg daily (QD), once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Interventions

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Cinacalcet

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg daily (QD), once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Intervention Type DRUG

Placebo

Possible doses: 30, 60, 90, 120, and 180 mg using tablet strengths of 30, 60, or 90 mg. Sequential titration starting at 30 mg QD, once every 4 weeks for the first 20 weeks and once every 8 weeks after Week 20. Titration increases or decreases based on PTH values, serum calcium, and safety. Daily dosing unless temporary hold criteria or withdrawal criteria is met, or until study completion; estimated 2.5 to 4 years of intervention.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Inclusion:≥ 18 years of age
* Treated with maintenance hemodialysis - PTH ≥ 300 pg/mL (31.8 pmol/L)
* serum calcium ≥ 8.4mg/dL (2.1 mmol/L)
* Ca x P ≥ 45 mg2\*/dL2 (3.63 mmol2/L2)

Exclusion Criteria

* Parathyroidectomy in the 12 weeks before the date of informed consent
* Received therapy with cinacalcet within 3 months of randomization
* Hospitalization within 12 weeks of randomization for any of the following events: a. Myocardial ischemia b. Unstable angina c. Heart Failure (HF) (including any unplanned presentation to a health care facility that would require mechanical intervention \[i.e., unplanned dialysis treatment\]) d. Peripheral vascular disease (other than dialysis vascular access revision) e. Stroke
* History of seizure within 12 weeks prior to randomization
* Scheduled date for kidney transplant from a known living donor
* Anticipated parathyroidectomy within 6 months after randomization

* in all instances, the 2 refers to squared.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

References

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Chertow GM, Correa-Rotter R, Block GA, Drueke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Wheeler DC, Parfrey PS. Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial. Nephrol Dial Transplant. 2012 Jul;27(7):2872-9. doi: 10.1093/ndt/gfr777. Epub 2012 Apr 23.

Reference Type BACKGROUND
PMID: 22529163 (View on PubMed)

Chertow GM, Pupim LB, Block GA, Correa-Rotter R, Drueke TB, Floege J, Goodman WG, London GM, Mahaffey KW, Moe SM, Wheeler DC, Albizem M, Olson K, Klassen P, Parfrey P. Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol. 2007 Sep;2(5):898-905. doi: 10.2215/CJN.04381206. Epub 2007 Aug 16.

Reference Type BACKGROUND
PMID: 17702710 (View on PubMed)

EVOLVE Trial Investigators; Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012 Dec 27;367(26):2482-94. doi: 10.1056/NEJMoa1205624. Epub 2012 Nov 3.

Reference Type BACKGROUND
PMID: 23121374 (View on PubMed)

Parfrey PS, Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J, Herzog CA, London GM, Mahaffey KW, Moe SM, Wheeler DC, Dehmel B, Trotman ML, Modafferi DM, Goodman WG. The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial. J Clin Endocrinol Metab. 2013 Dec;98(12):4834-44. doi: 10.1210/jc.2013-2975. Epub 2013 Oct 9.

Reference Type BACKGROUND
PMID: 24108314 (View on PubMed)

Floege J, Tsirtsonis K, Iles J, Drueke TB, Chertow GM, Parfrey P. Incidence, predictors and therapeutic consequences of hypocalcemia in patients treated with cinacalcet in the EVOLVE trial. Kidney Int. 2018 Jun;93(6):1475-1482. doi: 10.1016/j.kint.2017.12.014. Epub 2018 Mar 7.

Reference Type DERIVED
PMID: 29525393 (View on PubMed)

Abdalla S, Montez-Rath ME, Parfrey PS, Chertow GM. The win ratio approach to analyzing composite outcomes: An application to the EVOLVE trial. Contemp Clin Trials. 2016 May;48:119-24. doi: 10.1016/j.cct.2016.04.001. Epub 2016 Apr 11.

Reference Type DERIVED
PMID: 27080930 (View on PubMed)

Moe SM, Chertow GM, Parfrey PS, Kubo Y, Block GA, Correa-Rotter R, Drueke TB, Herzog CA, London GM, Mahaffey KW, Wheeler DC, Stolina M, Dehmel B, Goodman WG, Floege J; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators*. Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Circulation. 2015 Jul 7;132(1):27-39. doi: 10.1161/CIRCULATIONAHA.114.013876. Epub 2015 Jun 9.

Reference Type DERIVED
PMID: 26059012 (View on PubMed)

Floege J, Kubo Y, Floege A, Chertow GM, Parfrey PS. The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial. Clin J Am Soc Nephrol. 2015 May 7;10(5):800-7. doi: 10.2215/CJN.10221014. Epub 2015 Apr 17.

Reference Type DERIVED
PMID: 25887067 (View on PubMed)

Kubo Y, Sterling LR, Parfrey PS, Gill K, Mahaffey KW, Gioni I, Trotman ML, Dehmel B, Chertow GM. Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial. Pharm Stat. 2015 May-Jun;14(3):242-51. doi: 10.1002/pst.1680. Epub 2015 Apr 6.

Reference Type DERIVED
PMID: 25851955 (View on PubMed)

Parfrey PS, Drueke TB, Block GA, Correa-Rotter R, Floege J, Herzog CA, London GM, Mahaffey KW, Moe SM, Wheeler DC, Kubo Y, Dehmel B, Goodman WG, Chertow GM; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators. The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Clin J Am Soc Nephrol. 2015 May 7;10(5):791-9. doi: 10.2215/CJN.07730814. Epub 2015 Feb 20.

Reference Type DERIVED
PMID: 25710802 (View on PubMed)

Wheeler DC, London GM, Parfrey PS, Block GA, Correa-Rotter R, Dehmel B, Drueke TB, Floege J, Kubo Y, Mahaffey KW, Goodman WG, Moe SM, Trotman ML, Abdalla S, Chertow GM, Herzog CA; EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial Investigators. Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc. 2014 Nov 17;3(6):e001363. doi: 10.1161/JAHA.114.001363.

Reference Type DERIVED
PMID: 25404192 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20050182

Identifier Type: -

Identifier Source: org_study_id

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