Chronic Kidney Diseases, High Cholesterol
Conditions
Brief summary
110 individuals with stage 4-5 Chronic Kidney Disease (CKD) will be randomized to 1-year of blinded Evolocumab or placebo. Subjects will undergo evaluation of circulating lipids at baseline and end of study. A substudy including 50 subjects will assess myocardial rest and stress positron emission tomography (PET) at baseline and at 1-year.
Detailed description
The purpose of this study is to evaluate the effect of evolocumab (Repatha®)-a Food and Drug Administration (FDA)-approved biological drug that has been shown to reduce LDL cholesterol (bad cholesterol) Early data show that the beneftis of evolocumab may be increased as kidney function declines. This trial is therefore designed to provide additional evidence regarding the safety and cholesterol-lowering effects of evolocumab compared with placebo, a pill that has no therapeutic effect, in advanced CKD patients.
Interventions
DRUGEvolocumab
Evolocumab is commercially available in the United States and is manufactured by Amgen. Drug and placebo, will be supplied by the manufacturer. The SureClick® pre-filled auto injector contain Evolocumab (140 mg) acetate (1.2 mg), polysorbate 80 (0.1 mg), proline (25 mg) in water for Injection. Evolocumab will be administered at a dose of 420 mg subcutaneously once monthly.
OTHERPlacebo
Placebo will be supplied by the manufacturer. Placebo auto injectors will be identically packaged but will lack the active ingredient. Placebo will be administered at an equivalent volume to Evolocumab and given subcutaneously once monthly.
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* CKD Stage 4-5 defined as * eGFR ≤30 mL/min/1.73m2 on screening lab OR * Treatment with maintenance hemodialysis for at least 30 days prior to screening * LDL ≥70 mg/dL and * Treatment with maximal tolerated doses of a statin OR * Statin intolerance defined as any history of intolerance or allergy to ≥1 statin * Age 40-80 years * Individuals ≤60 years old are required to have ≥1 of the following cardiovascular risk factors: * History of CV disease * History of peripheral vascular disease * Diabetes * Smoking * Baseline LDL ≥160 mg/dL * Macroalbuminuria (albumin to creatinine ratio ≥300 mg/g on spot sample)
Exclusion criteria
* Age \>80 years * Expected survival \< 1 year * Transplant expected within \< 1 year * Active liver disease (history of cirrhosis, ALT or AST \> 2x ULN) * CPK \> 5x ULN at screening * Malignancy within 5 years except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma * Subject has received drugs that are strong inhibitors of cytochrome P-450 3A4 within 1 month prior to randomization or is likely to require such treatment during the study period * Currently enrolled in another interventional study * Female subject who has not used at least (1) effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal. * Effective measures of birth control include surgical sterilization, barrier methods, hormonal contraceptives and intrauterine devices. * Pregnant or breast-feeding subjects * Known sensitivity or intolerance to study medications The following additional criteria will be utilized to exclude individuals from participating in the PET substudy: * Severe asthma or obstructive lung disease defined by * Hospitalization for asthma or obstructive lung disease within 8 weeks * Use of oral steroids for lung disease within 8 weeks * Chronic oxygen therapy * Use of rescue inhalers ≥three times weekly in the previous 4 weeks * History of seizures * Second or third-degree AV block, unless a functioning pacemaker is present * Sinus node dysfunction unless a functioning pacemaker is present
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change in LDL cholesterol concentration | Baseline, Week 52 | The primary endpoint is selected to evaluate the key pharmacologic mechanism underlying Evolocumab's cardiovascular benefits. This will be analyzed with Lipid parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events (SAEs) | Baseline, Week 52 | — |
| Change in coronary flow reserve (CFR) | Baseline, Week 52 | Change in coronary flow reserve (CFR), the key secondary efficacy endpoint, is a measure of overall cardiovascular health.This test provides an integrative measure of myocardial microvascular supply and myocardial endothelial function as well as large vessel coronary flow. Change in coronary flow reserve over one year as measured by cardiac PET scanning. |
Countries
United States
Outcome results
None listed