Alirocumab in Patients With Acute Myocardial Infarction
Condition: Myocardial Infarction; Hypercholesterolemia
MeSH terms: Myocardial Infarction; Hypercholesterolemia; Infarction
Intervention: alirocumab; placebo
Intervention MeSH terms: Alirocumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Myocardial Infarction; Low Density Lipoprotein Cholesterol; proprotein convertase subtilisin kexin 9, human; alirocumab

Summary:

      Phase IV investigator initiated clinical trial to study the effectiveness of alirocumab, an
      inhibitor of proprotein convertase subtilisin/kexin (PCSK9), versus placebo added to
      high-intensity statin (atorvastatin 80 mg) in lowering low density lipoprotein (LDL)
      cholesterol during non-ST segment elevation myocardial infarction (NSTEMI).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Acute type I (spontaneous) NSTEMI defined as chest pain (or equivalent) with an onset
             of symptoms within 12 hours of presentation, a duration of >15 minutes, and elevated
             cardiac troponin I levels, with or without electrocardiographic changes [with the
             exclusion of ST elevation];

          2. On medical therapy with high intensity statin prior to admission (either atorvastatin
             40-80 mg or rosuvastatin 20-40 mg) as documented by hospital or pharmacy records and
             with known LDL cholesterol ≥70 mg/dL within the prior 12 months.

        Exclusion Criteria:

          1. Age <21 years of age

          2. Inability to give informed consent

          3. Previous, current or planned treatment with a PCSK9 inhibitor

          4. Known history of loss of function of PCSK9 (genetic mutation or sequence variation)

          5. Patient with homozygous familial hypercholesterolemia (clinically or by previous
             genotyping)

          6. Recent (<14 days) or active use of immunosuppressive drugs (including but not limited
             to high-dose corticosteroids [>1mg/kg of prednisone equivalent], Tumor Necrosis
             Factor-α blockers, cyclosporine) not including non-steroidal antinflammatory drugs or
             corticosteroids used for IV dye allergy or corticosteroids used as replacement therapy
             for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to
             randomization (note: topical, intra-articular, nasal, inhaled, and ophthalmic steroid
             therapies are not considered "systemic" and are allowed);

          7. Chronic auto-immune or auto-inflammatory disease (including but not limited to
             rheumatoid arthritis, systemic lupus erythematosus);

          8. History of cancer within the past 5 years, except for adequately treated basal cell
             skin cancer, squamous cell skin cancer, or in situ cervical cancer;

          9. Known chronic hepatitis B or C infection (excluding patients with a positive antibody
             who were successfully treated or who have demonstrated no viral load);

         10. Known human immunodeficiency virus infection.

         11. Use of fibrates other than fenofibrate within 6 weeks of the screening visit.

         12. Uncontrolled hypothyroidism. Note: patients on thyroid replacement therapy can be
             included if the dosage of thyroxin has been stable for at least 12 weeks prior to
             screening.

         13. Known history of a hemorrhagic stroke.

         14. Has been previously treated with at least 1 dose of alirocumab or any other anti-PCSK9
             monoclonal antibody in other clinical studies.

         15. Conditions/situations such as:

               1. Any clinically significant abnormality identified at the time of screening that
                  in the judgment of the investigator or any sub-investigator would preclude safe
                  completion of the study or constrain assessment of endpoints, such as major
                  systemic diseases or patients with short life expectancy.

               2. Patients considered by the investigator or any sub-investigator to be
                  inappropriate for this study for any reason:

             i. Those patients deemed unable to meet specific protocol requirements, such as
             scheduled visits.

             ii. Those patients the investigator deems unable to administer or tolerate long-term
             injections.

             c. Investigator or any sub-investigator, pharmacist, study coordinator, other study
             staff, or relative thereof directly involved in the conduct of the protocol.

             d. Presence of any other conditions (geographic or social), actual or anticipated,
             that the investigator feels would restrict or limit the patient's participation for
             the duration of the study.

         16. Thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or > upper limit of
             normal (ULN); if TSH is abnormal due to controlled hypothyroidism (patient is on a
             stable dose of thyroid replacement therapy), the patient may be enrolled into the
             study;

         17. Exclusion Criteria Related to the Active Comparator and/or Mandatory Background
             Therapies: All contraindications to the background therapies or warnings/precautions
             of use (when appropriate) as displayed in the respective national product labeling.

         18. Exclusion Criteria Related to the Current Knowledge of Alirocumab

               1. Known hypersensitivity to monoclonal antibody therapeutics

               2. Pregnant or breastfeeding women

         19. Women of childbearing potential who are not protected by highly effective method(s) of
             birth control throughout the entire duration of study treatment and for 10 weeks after
             the last dose of study drug and/or who are unwilling or unable to be tested for
             pregnancy.

         20. Men capable of impregnating women who are not protected by highly effective method(s)
             of birth control and/or who are unwilling to use an effective contraceptive method
             throughout the entire duration of study treatment and for 10 weeks after the last dose
             of study drug.