Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study (DESCARTES)

Amgen

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: Atorvastatin; Biological: Placebo; Biological: Evolocumab; Other: Diet Only; Drug: Ezetimibe

Study type: Interventional

Funder types: Industry

Identifiers

NCT01516879

20110109

Details and patient eligibility

About

To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.

Full description

Eligible participants with screening central laboratory low-density lipoprotein cholesterol (LDL-C) values ≥ 75 mg/dL (1.9 mmol/L) were instructed to follow National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) Therapeutic Lifestyle Changes (TLC) diet and were assigned to 1 of the following 4 background lipid-lowering therapies for a 4-week stabilization period based upon their screening LDL-C and its distance from the individual's required goal as stipulated by their NCEP ATP III risk category:

1. no drug therapy required - diet alone
2. low dose drug therapy required - diet plus atorvastatin 10 mg orally (PO) once daily (QD)
3. high dose drug therapy required - diet plus atorvastatin 80 mg PO QD
4. maximal drug therapy required - diet plus atorvastatin 80 mg PO QD plus ezetimibe 10 mg PO QD.

If the participant met entry criteria at the end of the lipid stabilization period they were randomized 2:1 to receive evolocumab 420 mg or placebo subcutaneously once a month for 52 weeks in addition to their background therapy.

Enrollment: 905 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject has provided informed consent.

• Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:

  • < 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent
  • < 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
  • OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD

• Fasting triglycerides ≤ 400 mg/dL

Exclusion criteria

• New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction < 30%
• Uncontrolled cardiac arrhythmia
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes
• Uncontrolled hypertension

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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905 participants in 2 patient groups, including a placebo group

Evolocumab

Experimental group

Description:

Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

Treatment:

Drug: Atorvastatin

Other: Diet Only

Drug: Ezetimibe

Biological: Evolocumab

Placebo

Placebo Comparator group

Description:

Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

Treatment:

Drug: Atorvastatin

Other: Diet Only

Drug: Ezetimibe

Biological: Placebo