Clinical trial NCT00345839: E.V.O.L.V.E. Trial™: EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events
Official title: EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease
Keywords: Cinacalcet HCl
Cinacalcet
AMG 073
Sensipar
Mimpara
Calcimimetic
Hemodialysis
CKD
Secondary hyperparathyroidism (HPT)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-06-29
Enrollment: 3883
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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)

Eligibility criteria: 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: - Exclusion:

* 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.

Primary outcomes:
measure: Time to Primary Composite Endpoint (All-cause Mortality, Myocardial Infarction, Hospitalization for Unstable Angina, Heart Failure or Peripheral Vascular Event)
timeFrame: From date of randomization until date of first confirmed primary composite endpoint event, assessed up to 5.4 years
Secondary outcomes:
measure: Time to All-cause Mortality
timeFrame: From date of randomization until date of confirmed all-cause mortality endpoint event, assessed up to 5.4 years
measure: Time to Myocardial Infarction
timeFrame: From date of randomization until date of first confirmed myocardial infarction endpoint event, assessed up to 5.4 years
measure: Time to Hospitalization for Unstable Angina
timeFrame: From date of randomization until date of first confirmed hospitalization for unstable angina endpoint event, assessed up to 5.4 years
measure: Time to Heart Failure
timeFrame: From date of randomization until date of first confirmed heart failure endpoint event, assessed up to 5.4 years
measure: Time to Peripheral Vascular Event
timeFrame: From date of randomization until date of first confirmed peripheral vascular endpoint event, assessed up to 5.4 years
measure: Time to Cardiovascular Mortality
timeFrame: From date of randomization until date of first confirmed cardiovascular mortality endpoint event, assessed up to 5.4 years
measure: Time to Stroke
timeFrame: From date of randomization until date of first confirmed stroke endpoint event, assessed up to 5.4 years
measure: Time to Bone Fracture
timeFrame: From date of randomization until date of first confirmed bone fracture endpoint event, assessed up to 5.4 years
measure: Time to Parathyroidectomy
timeFrame: From date of randomization until date of first confirmed parathyroidectomy endpoint event, assessed up to 5.4 years
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.