Evolocumab In Advanced Chronic Kidney Disease Trial (EVO-CKD)

NYU Langone Health

Status and phase

Withdrawn

Phase 4

Conditions

Chronic Kidney Diseases

High Cholesterol

Treatments

Other: Placebo

Drug: Evolocumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04510844

20-00405

21-00455 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

40 to 80 years old

Volunteers

No Healthy Volunteers

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