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

Phase 3
Completed
Conditions
Secondary Hyperparathyroidism
Chronic Kidney Disease
Interventions
Drug: Placebo
Registration Number
NCT00345839
Lead Sponsor
Amgen
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)

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
3883
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
CinacalcetCinacalcet-
Primary Outcome Measures
NameTimeMethod
Time to Primary Composite Endpoint (All-cause Mortality, Myocardial Infarction, Hospitalization for Unstable Angina, Heart Failure or Peripheral Vascular Event)From date of randomization until date of first confirmed primary composite endpoint event, assessed up to 5.4 years

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.

Secondary Outcome Measures
NameTimeMethod
Time to Myocardial InfarctionFrom date of randomization until date of first confirmed myocardial infarction endpoint event, assessed up to 5.4 years

Time to Myocardial Infarction. Stratified by history of diabetes and country.

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

Time to Heart Failure. Stratified by history of diabetes and country.

Time to Peripheral Vascular EventFrom date of randomization until date of first confirmed peripheral vascular endpoint event, assessed up to 5.4 years

Time to Peripheral Vascular Event. Stratified by history of diabetes and country.

Time to Bone FractureFrom date of randomization until date of first confirmed bone fracture endpoint event, assessed up to 5.4 years

Time to Bone Fracture. Stratified by history of diabetes and country.

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

Time to All-cause Mortality. Stratified by history of diabetes and country.

Time to StrokeFrom date of randomization until date of first confirmed stroke endpoint event, assessed up to 5.4 years

Time to Stroke. Stratified by history of diabetes and country.

Time to Hospitalization for Unstable AnginaFrom date of randomization until date of first confirmed hospitalization for unstable angina endpoint event, assessed up to 5.4 years

Time to Hospitalization for Unstable Angina. Stratified by history of diabetes and country.

Time to Cardiovascular MortalityFrom date of randomization until date of first confirmed cardiovascular mortality endpoint event, assessed up to 5.4 years

Time to Cardiovascular Mortality. Stratified by history of diabetes and country.

Time to ParathyroidectomyFrom date of randomization until date of first confirmed parathyroidectomy endpoint event, assessed up to 5.4 years

Time to Parathyroidectomy. Stratified by history of diabetes and country.

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