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Evolocumab Plus Ezetimibe in Haemodialized Statin-intolerant Patients With Hypercholesterolemia

Primary Purpose

Hypercholesterolemia, CKD Stage 5, Chronic Kidney Disease Requiring Chronic Dialysis

Status

Unknown status

Phase

Phase 4

Locations

Italy

Study Type

Interventional

Intervention

Evolocumab

Ezetimibe

Placebo

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring Hypercholesterolemia, Chronic Dialysis, Statin intollerant patients, LDL reduction, Cardiovascular risk

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Policlinico CasilinoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Evolocumab + Ezetimibe

Placebo + Ezetimibe

Arm Description

Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Outcomes

Primary Outcome Measures

LDL cholesterol change dichotomic

proportion of patients that achieve an LDL cholesterol level < 55 mg/dL

Secondary Outcome Measures

LDL cholesterol change time-points

change in LDL cholesterol levels from baseline

HDL cholesterol change

change in HDL cholesterol levels from baseline

non-HDL cholesterol change

change in non-HDL cholesterol levels from baseline

Triglycerides change

change in triglycerides levels from baseline

Full Information

NCT ID

NCT04659525

First Posted

December 2, 2020

Last Updated

December 13, 2020

Sponsor

Policlinico Casilino ASL RMB

Collaborators

IRCCS San Raffaele

1. Study Identification

Unique Protocol Identification Number

NCT04659525

Brief Title

Evolocumab Plus Ezetimibe in Haemodialized Statin-intolerant Patients With Hypercholesterolemia

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Unknown status

Study Start Date

November 1, 2020 (Actual)

Primary Completion Date

November 30, 2021 (Anticipated)

Study Completion Date

December 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Policlinico Casilino ASL RMB

Collaborators

IRCCS San Raffaele

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia, CKD Stage 5, Chronic Kidney Disease Requiring Chronic Dialysis

Keywords

Hypercholesterolemia, Chronic Dialysis, Statin intollerant patients, LDL reduction, Cardiovascular risk

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Evolocumab + Ezetimibe

Arm Type

Experimental

Arm Description

Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Arm Title

Placebo + Ezetimibe

Arm Type

Placebo Comparator

Arm Description

Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Intervention Type

Drug

Intervention Name(s)

Evolocumab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ezetimibe

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

LDL cholesterol change dichotomic

Description

proportion of patients that achieve an LDL cholesterol level < 55 mg/dL

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

LDL cholesterol change time-points

Description

change in LDL cholesterol levels from baseline

Time Frame

4 weeks, 12 weeks, 24 weeks

Title

HDL cholesterol change

Description

change in HDL cholesterol levels from baseline

Time Frame

24 weeks

Title

non-HDL cholesterol change

Description

change in non-HDL cholesterol levels from baseline

Time Frame

24 weeks

Title

Triglycerides change

Description

change in triglycerides levels from baseline

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gennaro Cice, MD

Phone

0039330915294

gennarocice@hormail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Leonardo Calò, MD

Phone

0623188406

leonardocalo.doc@gmail.com

Facility Information:

Facility Name

Policlinico Casilino

City

Rome

ZIP/Postal Code

00169

Country

Italy

Individual Site Status

Recruiting

Facility Contact: