Evolocumab Plus Ezetimibe in Haemodialized Statin-intolerant Patients With Hypercholesterolemia
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| ClinicalTrials.gov Identifier: NCT04659525 |
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Recruitment Status :
Recruiting
First Posted : December 9, 2020
Last Update Posted : December 17, 2020
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Sponsor:
Policlinico Casilino ASL RMB
Collaborator:
IRCCS San Raffaele
Information provided by (Responsible Party):
Leonardo Calò, MD, Policlinico Casilino ASL RMB
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypercholesterolemia CKD Stage 5 Chronic Kidney Disease Requiring Chronic Dialysis | Drug: Evolocumab Drug: Ezetimibe Drug: Placebo | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 50 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | November 1, 2020 |
| Estimated Primary Completion Date : | November 30, 2021 |
| Estimated Study Completion Date : | December 30, 2021 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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
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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) |
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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
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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 |
Primary Outcome Measures :
- LDL cholesterol change dichotomic [ Time Frame: 24 weeks ]proportion of patients that achieve an LDL cholesterol level < 55 mg/dL
Secondary Outcome Measures :
- LDL cholesterol change time-points [ Time Frame: 4 weeks, 12 weeks, 24 weeks ]change in LDL cholesterol levels from baseline
- HDL cholesterol change [ Time Frame: 24 weeks ]change in HDL cholesterol levels from baseline
- non-HDL cholesterol change [ Time Frame: 24 weeks ]change in non-HDL cholesterol levels from baseline
- Triglycerides change [ Time Frame: 24 weeks ]change in triglycerides levels from baseline
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| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04659525
Contacts
| Contact: Gennaro Cice, MD | 0039330915294 | gennarocice@hormail.com | |
| Contact: Leonardo Calò, MD | 0623188406 | leonardocalo.doc@gmail.com |
Locations
| Italy | |
| Policlinico Casilino | Recruiting |
| Rome, Italy, 00169 | |
| Contact: Leonardo Calò, MD 00393388589677 leonardocalo.doc@gmail.com | |
| Contact: Luca Monzo, MD, PhD 00393460242037 luca.monzo@uniroma1.it | |
| Principal Investigator: Gennaro Cice, MD | |
| Sub-Investigator: Luca Monzo, MD, PhD | |
| Principal Investigator: Maurizio Volterrani, MD | |
| Principal Investigator: Leonardo Calò, MD | |
Sponsors and Collaborators
Policlinico Casilino ASL RMB
IRCCS San Raffaele
Publications:
| Responsible Party: | Leonardo Calò, MD, Head of Cardiology Department, Policlinico Casilino ASL RMB |
| ClinicalTrials.gov Identifier: | NCT04659525 |
| Other Study ID Numbers: |
Evolocumab02 |
| First Posted: | December 9, 2020 Key Record Dates |
| Last Update Posted: | December 17, 2020 |
| Last Verified: | December 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| 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 |
Keywords provided by Leonardo Calò, MD, Policlinico Casilino ASL RMB:
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Hypercholesterolemia Chronic Dialysis Statin intollerant patients LDL reduction Cardiovascular risk |
Additional relevant MeSH terms:
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Kidney Diseases Renal Insufficiency, Chronic Hypercholesterolemia Urologic Diseases Renal Insufficiency Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders |
Metabolic Diseases Ezetimibe Evolocumab Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents |