PCSK 9 Inhibition as Secondary Prevention in Renal Transplant Patients

• Status: Completed
• Trial end date: 2020-05-01
• Target enrollment: 0
• Participant gender: All

Summary

From this randomized controlled study, we aim to:

A.Do do cardiovascular risk stratification of renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait.

B. To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs. maximum tolerated statin therapy alone in the reduction of major cardiovascular events among renal transplant recipients with cardiovascular disease.

C. To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs. maximum tolerated statin therapy alone in terms of LDL-C-lowering, muscle symptoms, and quality of life.

D. To compare patient adherence to the different treatment protocols.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hamid Al-Essa Organ Transplant Center
• Treatments: Evolocumab

Criteria

Inclusion Criteria:

• 1. Signed informed consent, 2. Male or female Kuwaiti older than 30 and younger than ≤ 80 years of age at the signing of informed consent 3. History of clinically evident cardiovascular disease(diagnosis of myocardial infarction; non-hemorrhagic stroke or symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with the ankle-brachial index (ABI) < 0.85, or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease, 4. At least 1 major risk factor or at least 2 minor risk factors below: Major Risk Factors (1 Required): o diabetes (type 1 or type 2) o age ≥ 65 years at randomization (and ≤ 85 years at the time of informed consent) o MI or non-hemorrhagic stroke within 6 months of screening o additional diagnosis of myocardial infarction or non-hemorrhagic stroke excluding qualifying MI or non-hemorrhagic stroke o current daily cigarette smoking o history of symptomatic PAD (as mentioned before) if eligible by MI or stroke history; Minor Risk Factors (2 Required): o history of non-MI related coronary revascularization o residual coronary artery disease with ≥ 40% stenosis in ≥ 2 large vessels o Most recent HDL-C <1.0 mmol/L for men and <1.3 mmol/L for women by the central laboratory before randomization o Most recent CRP > 2.0 mg/L by the central laboratory before randomization o Most recent LDL-C ≥ 3.4 mmol/L or non-HDL-C ≥ 4.1 mmol/L by the central laboratory before randomization o metabolic syndrome.

Exclusion Criteria:

• Exclusion Criteria:

1. Recent MI or stroke 2. NYHA class III or IV, or last known left ventricular ejection fraction < 30% 3. Known hemorrhagic stroke at any time 4. Uncontrolled or recurrent ventricular tachycardia 5. Planned or expected cardiac surgery or revascularization within 3 months after randomization 6. Uncontrolled hypertension (sitting systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg), 7. Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab < 12 weeks prior to final lipid screening 8. Untreated or inadequately treated hyperthyroidism or hypothyroidism (thyroid-stimulating hormone (TSH) < lower limit of normal or > 1.5 times the upper limit of normal and free thyroxine (T4) levels that are outside normal range at the final screening. ,9. Severe renal graft dysfunction(estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 at final screening, 10. Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN as determined by central laboratory analysis at the final screening. 11. Personal or family history of hereditary muscular disorders. 12. Malignancy or HIV patients,

13. Known major active infection or major hematologic, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator,

13. Female subject who has either (1) not used-acceptable method(s) of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment with IP and for an additional 15 weeks after the end of treatment with IP unless the subject is sterilized or postmenopausal; 23. Known sensitivity to any of the active substances or their excipients to be administered during dosing.