PCSK 9 Inhibition as Secondary Prevention in Renal Transplant Patients

NCT04665830 | Completed Phase 3 DMC

• 1 other identifier: 2018/789
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kideny Transplant Recipients With High Cardiovascular Risk Score

Outcome Measures

Primary Outcomes (1)

• Any major cardiovascular events

  cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization

  24 months

Study Arms (2)

Group 1

ACTIVE COMPARATOR

Evolocumab group, patients who are receiving this therapy for 12 months.

Drug: Evolocumab

Group 2

PLACEBO COMPARATOR

The Statin group includes patients who are maintained on statin therapy.

Drug: Evolocumab

Interventions

Evolocumab DRUG

treated patients with evolocumab for high cholesterol

Group 1; Group 2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hamid Al-Essa Organ Transplant Center: lead

Study Sites (1)

OTC, MOH , Kuwait

Kuwait City, Kuwait, Kuwait

Location

MeSH Terms

Interventions

evolocumab

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant nephrologist

Model Details: all renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait for 6 months duration. Cardio-vascular risk score will be estimated using the Framingham score. Patients with scores higher than 10 will be randomized in this prospective controlled study to receive either the evolocumab (group 1, n=100 patients) or the conventional group (group 2, n=100 patients).

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: May 1, 2018
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: December 14, 2020

Record last verified: 2020-12

Locations

KU (1)