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

NCT00345839 | Completed Phase 3 Results DMC

• 1 other identifier: 20050182
• Study Type: interventional
• Target: 3,883
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Secondary Hyperparathyroidism; Chronic Kidney Disease

Keywords

Cinacalcet HCl; Cinacalcet; AMG 073; Sensipar; Mimpara; Calcimimetic; Hemodialysis; CKD; Secondary hyperparathyroidism (HPT)

Outcome Measures

Primary Outcomes (1)

• Time to Primary Composite Endpoint (All-cause Mortality, Myocardial Infarction, Hospitalization for Unstable Angina, Heart Failure or Peripheral Vascular Event)

  Time to Primary Composite Endpoint (All-cause Mortality, Myocardial Infarction, Hospitalization for Unstable Angina, Heart Failure or Peripheral Vascular Event). Stratified by history of diabetes and country.

  From date of randomization until date of first confirmed primary composite endpoint event, assessed up to 5.4 years

Secondary Outcomes (9)

• Time to All-cause Mortality

  From date of randomization until date of confirmed all-cause mortality endpoint event, assessed up to 5.4 years

• Time to Myocardial Infarction

  From date of randomization until date of first confirmed myocardial infarction endpoint event, assessed up to 5.4 years

• Time to Hospitalization for Unstable Angina

  From date of randomization until date of first confirmed hospitalization for unstable angina endpoint event, assessed up to 5.4 years

• Time to Heart Failure

  From date of randomization until date of first confirmed heart failure endpoint event, assessed up to 5.4 years

• Time to Peripheral Vascular Event

  From date of randomization until date of first confirmed peripheral vascular endpoint event, assessed up to 5.4 years

Study Arms (2)

Cinacalcet

EXPERIMENTAL

Drug: Cinacalcet

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Cinacalcet 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.

Cinacalcet

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Related Publications (11)

• 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.

  PMID: 22529163 BACKGROUND

• 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.

  PMID: 17702710 BACKGROUND

• 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.

  PMID: 23121374 BACKGROUND

• 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.

  PMID: 24108314 BACKGROUND

• 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.

  PMID: 29525393 DERIVED

• 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.

  PMID: 27080930 DERIVED

• 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.

  PMID: 26059012 DERIVED

• 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.

  PMID: 25887067 DERIVED

• 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.

  PMID: 25851955 DERIVED

• 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.

  PMID: 25710802 DERIVED

• 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.

  PMID: 25404192 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic

Interventions

Cinacalcet

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2006
• First Posted: June 29, 2006
• Study Start: August 22, 2006
• Primary Completion: April 10, 2012
• Study Completion: April 10, 2012
• Last Updated: November 7, 2022
• Results First Posted: January 22, 2014

Record last verified: 2022-11