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

Amgen3,883 enrolled

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

3,883

Conditions

Secondary Hyperparathyroidism Chronic Kidney Disease

Interventions

CinacalcetDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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

Secondary Outcomes

Time to All-cause Mortality

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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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