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

Study Overview
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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)

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

Conditions
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Chronic Kidney Disease, Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: Cinacalcet
* Drug: Placebo


Participation Criteria
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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: - 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cinacalcet<br> | Drug: Cinacalcet<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cinacalcet HCl, Cinacalcet, AMG 073, Sensipar, Mimpara, Calcimimetic, Hemodialysis, CKD, Secondary hyperparathyroidism (HPT)