Evolocumab Plus Ezetimibe in Haemodialized Statin-intolerant Patients With Hypercholesterolemia

December 13, 2020 updated by: Leonardo Calò, MD, Policlinico Casilino ASL RMB

Phase IV Study for Efficacy and Safety of Evolocumab Added to Ezetimibe (Standard of Care) in High Cardiovascular Risk Haemodialized Statin Intolerant Patients With Hypercholesterolemia

Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol, reducing in turn the risk of cardiovascular events. Whether evolcumab is effective in haemodialized patients is uncertain. The investigators will conduct a randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab in high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia. Patients will be randomly assigned to receive evolocumab (140 mg subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) or matching placebo (subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) for 24 weeks. The primary efficacy end point will be the proportion of patients that will reduce LDL-C < 55 mg/dL in the evolocumab group compared to placebo at 24 weeks. The key secondary efficacy end points will be: the reduction of LDL-C from baseline at 4, 6 and 12 weeks; the reduction of HDL-C, non-HDL cholesterol and triglycerides from baseline at 24 weeks. Every adverse event (serious and non-serious) correlated to drug infusion will be recorded (safety end-point).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00169
        • Recruiting
        • Policlinico Casilino
        • Contact:
        • Sub-Investigator:
          • Luca Monzo, MD, PhD

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 to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • high cardiovascular risk defined as patients with: Documented cardiovascular disease (CVD), clinical or unequivocal on imaging. Documented clinical CVD includes previous acute myocardial infarction, coronary revascularization and other arterial revascularization procedures, stroke and TIA, aortic aneurysm and PAD. Unequivocally documented CVD on imaging includes plaque on coronary angiography or carotid ultrasound; DM with target organ damage or with a major risk factor such as smoking or marked hypercholesterolaemia or marked hypertension.
  • History of statin intolerance, demonstrated by: trial of ≥2 statins with intolerance of any dose or to increase statin dose above the total maximum doses because of intolerable: Myopathy or myalgia (muscle pain, ache, or weakness without CK elevation), or Myositis (muscle symptoms with increased CK levels), or Rhabdomyolysis (muscle symptoms with marked CK elevation) and Resolution or improvement of symptoms when the statin dose was decreased or discontinued
  • patients with LDL-C >55 mg/dL
  • end-stage renal disease on chronic hemodialysis
  • Participant is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

  • secondary hypercholesterolemia (i.e. hypothyroidism, Primary biliary cholangitis, etc)
  • Use of drugs or dietary supplements that can impact on cholesterol value (i.e. progestinic, red yeast rice, niacin >200 mg/d, lipid-regulating drugs - eg, fibrates or derivatives, ezetimibe, bile-acid sequestrants, stanols, or stanol esters - )
  • Previous treatment with evolocumab or any other anti-PCSK9 therapy
  • Inability to provide informed consent or to attend follow-up visits
  • Unreliability as a study participant based on judgment of investigator's knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, psychosis)
  • Current enrollment in another investigational device or drug study or <30 d since ending another investigational device or drug study
  • serum triglycerides level > 400 mg/dL at baseline
  • Pregnancy, breastfeeding, or inadequate birth control in premenopausal female subjects
  • Laboratory values at screening CK >3 × ULN; AST or ALT >2 × ULN

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Evolocumab + Ezetimibe
Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
Drug: Evolocumab
In the intervention arm evolocumab 140 mg subcutaneous every 2 weeks will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia
Drug: Ezetimibe
Ezetimibe 10 mg daily will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia in both the placebo arm (plus placebo) and in the intervention arm (plus evolocumab)
PLACEBO_COMPARATOR: Placebo + Ezetimibe
Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
Drug: Ezetimibe
Ezetimibe 10 mg daily will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia in both the placebo arm (plus placebo) and in the intervention arm (plus evolocumab)
Drug: Placebo
In the placebo arm placebo subcutaneous every 2 weeks will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LDL cholesterol change dichotomic
Time Frame: 24 weeks
proportion of patients that achieve an LDL cholesterol level < 55 mg/dL
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LDL cholesterol change time-points
Time Frame: 4 weeks, 12 weeks, 24 weeks
change in LDL cholesterol levels from baseline
4 weeks, 12 weeks, 24 weeks
HDL cholesterol change
Time Frame: 24 weeks
change in HDL cholesterol levels from baseline
24 weeks
non-HDL cholesterol change
Time Frame: 24 weeks
change in non-HDL cholesterol levels from baseline
24 weeks
Triglycerides change
Time Frame: 24 weeks
change in triglycerides levels from baseline
24 weeks

Collaborators and Investigators

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

Sponsor

Policlinico Casilino ASL RMB

Collaborators

IRCCS San Raffaele

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

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)

November 1, 2020

Primary Completion (ANTICIPATED)

November 30, 2021

Study Completion (ANTICIPATED)

December 30, 2021

Study Registration Dates

First Submitted

December 2, 2020

First Submitted That Met QC Criteria

December 8, 2020

First Posted (ACTUAL)

December 9, 2020

Study Record Updates

Last Update Posted (ACTUAL)

December 17, 2020

Last Update Submitted That Met QC Criteria

December 13, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Evolocumab02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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