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
Sponsored by
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
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
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
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
No
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
Email
gennarocice@hormail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Leonardo Calò, MD
Phone
0623188406
Email
leonardocalo.doc@gmail.com
Facility Information:
Facility Name
Policlinico Casilino
City
Rome
ZIP/Postal Code
00169
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leonardo Calò, MD
Phone
00393388589677
Email
leonardocalo.doc@gmail.com
First Name & Middle Initial & Last Name & Degree
Luca Monzo, MD, PhD
Phone
00393460242037
Email
luca.monzo@uniroma1.it
First Name & Middle Initial & Last Name & Degree
Gennaro Cice, MD
First Name & Middle Initial & Last Name & Degree
Luca Monzo, MD, PhD
First Name & Middle Initial & Last Name & Degree
Maurizio Volterrani, MD
First Name & Middle Initial & Last Name & Degree
Leonardo Calò, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Evolocumab Plus Ezetimibe in Haemodialized Statin-intolerant Patients With Hypercholesterolemia
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