Evolocumab Plus Ezetimibe in High Risk Haemodialized Statin Intolerant Patients

Phase 4

• Conditions: Chronic Kidney Disease Requiring Chronic Dialysis; Hypercholesterolemia
• Interventions: Drug: Evolocumab; Drug: Placebo; Drug: Ezetimibe

• Registration Number: NCT04397653
• Lead Sponsor: Policlinico Casilino ASL RMB

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 reduction in LDL-C ≥ 20 mg/dL from baseline. 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; the number of patients achieving LDL-C \<70 mg/dL. Every adverse event (serious and non-serious) correlated to drug infusion will be recorded (safety end-point).

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-05
• Study Start: 2020-05-04
• Study First Submitted: 2020-05-12
• Study First Submitted QC: 2020-05-18
• Study First Posted: 2020-05-21
• Last Update Submitted: 2020-05-21
• Last Update Posted: 2020-05-26
• Primary Completion: 2020-11-19
• Study Completion: 2020-12-14

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

• LDL-C <70 mg/dL
• NYHA class III-IV heart failure or last known LVEF <30%
• Uncontrolled serious cardiac arrhythmia, defined as recurrent and highly symptomatic VT, AF with rapid ventricular response, or SVT that are not controlled by medications, within 3 months prior to randomization Planned cardiac surgery or revascularization DM, including: Type 1 DMType 2 DM that is poorly controlled (HbA1c>8.5%) or newly diagnosed within 6 months before randomization; Laboratory evidence of DM during screening (fasting serum glucose ≥126 mg/dL [7.0 mmol/L] or HbA1c≥6.5%) without prior DM diagnosis
• Uncontrolled hypertension, defined as sitting SBP >160mmHg or DBP>100 mm Hg
• Use during the 6 months before LDL-C screening of red yeast rice, niacin >200 mg/d, prescription lipid-regulating drugs (eg, fibrates or derivatives) other than statins, ezetimibe, bile-acid sequestrants, stanols, or stanol esters
• Use during the 12 months before LDL-C screening of a CETP inhibitor such as anacetrapib, dalcetrapib, or evacetrapib
• Use during the 3 months before LDL-C screening of systemic cyclosporine, systemic steroids excluding HRT, vitamin A derivatives (excluding vitamin Ain a multivitamin), or retinol derivatives for the treatment of dermatologic conditions
• Laboratory values at screening TSH < LLN or >1.5 × ULN; CK >3 × ULN; AST or ALT >2 × ULN
• Known concurrent illness within 3 months
• Infection
• Major hematologic, renal, metabolic, GI, or endocrine dysfunction in the judgment of the investigator
• DVT or PE
• Pregnancy, breastfeeding, or inadequate birth control in premenopausal female subjects
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Evolocumab + Ezetimibe	Ezetimibe	Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
Evolocumab + Ezetimibe	Evolocumab	Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
Placebo + Ezetimibe	Placebo	Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks
Placebo + Ezetimibe	Ezetimibe	Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Primary Outcome Measures

Name	Time	Method
LDL cholesterol reduction dichotomic	24 weeks	change in LDL cholesterol levels ≥ 20 mg/dL from baseline

Secondary Outcome Measures

Name	Time	Method
LDL cholesterol reduction time-points	4 weeks, 12 weeks, 24 weeks	change in LDL cholesterol levels from baseline
HDL cholesterol reduction	24 weeks	change in HDL cholesterol levels from baseline
non-HDL cholesterol reduction	24 weeks	change in non-HDL cholesterol levels from baseline
Triglycerides reduction	24 weeks	change in triglycerides levels from baseline
LDL cholesterol target achieving	24 weeks	percent of patients achieving an LDL cholesterol less than 70 mg/dL

Trial Locations

Locations (1)

Policlinico Casilino; 🇮🇹 Rome, Italy