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

November 3, 2022 updated by: Amgen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

3883

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: 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.
Experimental: Cinacalcet
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.

What is the study measuring?

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 Frame: 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.
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 Frame: From 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.
From date of randomization until date of confirmed all-cause mortality endpoint event, assessed up to 5.4 years
Time to Myocardial Infarction
Time Frame: From 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.
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 Frame: From 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.
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 Frame: From 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.
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 Frame: From 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.
From date of randomization until date of first confirmed peripheral vascular endpoint event, assessed up to 5.4 years
Time to Cardiovascular Mortality
Time Frame: From 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.
From date of randomization until date of first confirmed cardiovascular mortality endpoint event, assessed up to 5.4 years
Time to Stroke
Time Frame: From 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.
From date of randomization until date of first confirmed stroke endpoint event, assessed up to 5.4 years
Time to Bone Fracture
Time Frame: From 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.
From date of randomization until date of first confirmed bone fracture endpoint event, assessed up to 5.4 years
Time to Parathyroidectomy
Time Frame: From 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.
From date of randomization until date of first confirmed parathyroidectomy endpoint event, assessed up to 5.4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 22, 2006

Primary Completion (Actual)

April 10, 2012

Study Completion (Actual)

April 10, 2012

Study Registration Dates

First Submitted

June 27, 2006

First Submitted That Met QC Criteria

June 28, 2006

First Posted (Estimate)

June 29, 2006

Study Record Updates

Last Update Posted (Actual)

November 7, 2022

Last Update Submitted That Met QC Criteria

November 3, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20050182

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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