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

Chronic Kidney Disease Clinical Trial

— EVOLVE  

Official title:

EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00345839
• Other study ID #: 20050182
• Status: Completed
• Phase: Phase 3
• Start date: August 22, 2006
• Est. completion date: April 10, 2012

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3883
• Est. completion date: April 10, 2012
• Est. primary completion date: April 10, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Renal Insufficiency, Chronic
• Secondary Hyperparathyroidism

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (4)

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. — View 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. Epub 2007 Aug 16. — View Citation

EVOLVE Trial Investigators, Chertow GM, Block GA, Correa-Rotter R, Drüeke 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. — View Citation

Parfrey PS, Chertow GM, Block GA, Correa-Rotter R, Drüeke 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to All-cause Mortality	Time to All-cause Mortality. Stratified by history of diabetes and country.	From date of randomization until date of confirmed all-cause mortality endpoint event, assessed up to 5.4 years
Secondary	Time to Myocardial Infarction	Time to Myocardial Infarction. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed myocardial infarction endpoint event, assessed up to 5.4 years
Secondary	Time to Hospitalization for Unstable Angina	Time to Hospitalization for Unstable Angina. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed hospitalization for unstable angina endpoint event, assessed up to 5.4 years
Secondary	Time to Heart Failure	Time to Heart Failure. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed heart failure endpoint event, assessed up to 5.4 years
Secondary	Time to Peripheral Vascular Event	Time to Peripheral Vascular Event. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed peripheral vascular endpoint event, assessed up to 5.4 years
Secondary	Time to Cardiovascular Mortality	Time to Cardiovascular Mortality. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed cardiovascular mortality endpoint event, assessed up to 5.4 years
Secondary	Time to Stroke	Time to Stroke. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed stroke endpoint event, assessed up to 5.4 years
Secondary	Time to Bone Fracture	Time to Bone Fracture. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed bone fracture endpoint event, assessed up to 5.4 years
Secondary	Time to Parathyroidectomy	Time to Parathyroidectomy. Stratified by history of diabetes and country.	From date of randomization until date of first confirmed parathyroidectomy endpoint event, assessed up to 5.4 years

External Links

•   AmgenTrials clinical trials website