Effect of Secukinumab on Cardiorenal Outcomes in Patients With Cardiorenal Metabolic Syndrome and Atherosclerotic Cardiovascular Disease

Official title

A Prospective, Randomized, Open-Label, Parallel-Controlled Study to Evaluate the Efficacy and Safety of Targeted Interleukin-17A (IL-17A) Inhibitor (Secukinumab) on Cardiovascular and Renal Endpoints in Patients With Cardiorenal Metabolic Syndrome Complicated With Atherosclerotic Cardiovascular Disease

Overview

This is a prospective, randomized, open-label, parallel-controlled clinical trial to evaluate the efficacy and safety of targeted IL-17A inhibition with secukinumab on cardiovascular and renal endpoints in 100 patients with cardiorenal metabolic syndrome and atherosclerotic cardiovascular disease (ASCVD). Eligible subjects will be randomized 1:1 to receive either secukinumab 75 mg subcutaneous injection every 4 weeks for a total of 12 weeks plus standard guideline-directed medical therapy, or standard medical therapy alone. The primary endpoint is the time to first occurrence of 3-point major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) over a 2-year follow-up period. Key indicators include estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) for renal outcome assessment.

Interventions

• Biological Secukinumab (75 mg)
  75 mg, subcutaneous injection, once every 4 weeks for a total of 12 weeks
• Other Standard Medical Therapy
  Standard guideline-directed cardiovascular and renal protective therapy per clinical practice guidelines

Primary outcome measures

• Time to First Occurrence of 3-point Major Adverse Cardiovascular Events (MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) [Time frame: From randomization up to 2 years]

Secondary outcome measures (12)

• Time to first extended MACE composite endpoint [Time frame: From randomization up to 2 years]
• Total number of heart failure hospitalizations, urgent heart failure visits or cardiovascular death [Time frame: From randomization up to 2 years]
• All-cause mortality [Time frame: From randomization up to 2 years]
• Changes in carotid artery stenosis degree [Time frame: Baseline, Month 6, Month 24]
• Changes in carotid artery plaque size [Time frame: Baseline, Month 6, Month 24]
• Time to composite chronic kidney disease endpoint (sustained eGFR decline ≥30% or kidney failure) [Time frame: From randomization up to 2 years]
• Incidence of kidney failure (death due to renal failure, sustained eGFR <15 mL/min/1.73 m², or long-term renal replacement therapy) [Time frame: From randomization up to 2 years]
• Changes in UACR [Time frame: Baseline, Month 6, Month 24]
• Changes in eGFR [Time frame: Baseline, Month 6, Month 24]
• Annual slope of eGFR [Time frame: Baseline, Month 6, Month 24]
• Changes in high-sensitivity C-reactive protein (hs-CRP) [Time frame: Baseline, Month 6, Month 24]
• Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) [Time frame: Baseline, Month 6, Month 24]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years at screening.
• Meet at least one metabolic abnormality:

• Body mass index ≥ 23 kg/m²;
• Waist circumference ≥ 80 cm (female) or ≥ 90 cm (male);
• Fasting glucose 100-124 mg/dL (5.6-6.9 mmol/L) or glycated hemoglobin (HbA1c) 5.7-6.4%;
• Serum triglycerides ≥ 3.51 mmol/L;
• Documented hypertension, metabolic syndrome, or diabetes mellitus.
• Meet at least one diagnostic criterion for chronic kidney disease:

• eGFR ≥15 and <60 mL/min/1.73 m² (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] creatinine equation);
• UACR ≥ 200 mg/g with eGFR ≥ 60 mL/min/1.73 m² and documented albuminuria.
• Have documented atherosclerotic cardiovascular disease (at least one):

• Coronary heart disease: history of myocardial infarction, prior coronary revascularization, or ≥50% major epicardial coronary artery stenosis confirmed by cardiac catheterization or coronary coronary computed tomography angiography (CTA);
• Cerebrovascular disease: prior atherosclerotic stroke, prior carotid revascularization, or ≥50% carotid artery stenosis confirmed by imaging;
• Symptomatic peripheral artery disease.
• Able and willing to provide written informed consent.

Exclusion criteria

• Clinical evidence or suspected active infection judged by investigators.
• History of myocardial infarction, stroke, transient ischemic attack, or hospitalization for unstable angina within 60 days prior to randomization.
• Planned coronary, carotid, or peripheral artery revascularization at randomization.
• Major cardiac surgery, non-cardiac major surgery, or major endoscopy within 60 days before randomization, or planned major surgery during the study period.
• Current use of systemic immunosuppressive agents (glucocorticoids, small-molecule immunosuppressants, biologic DMARDs, anti-tumor drugs).
• Long-term intermittent hemodialysis or peritoneal dialysis.
• History or confirmed evidence of active tuberculosis.
• History of inflammatory bowel disease.
• Active malignancy or carcinoma in situ within the past 5 years.
• Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg).
• Chronic heart failure classified as New York Heart Association (NYHA) Class IV.
• History of bone marrow or solid organ transplantation, or planned organ transplantation during the study.
• Known or suspected allergy to secukinumab or related excipients.
• Pregnant, lactating females, or females of childbearing potential without adequate effective contraception.
• Absolute neutrophil count <2 ×10⁹/L or platelet count <120 ×10⁹/L, or alanine aminotransferase (ALT) / aspartate aminotransferase (AST) >2.5 × upper limit of normal.
• HbA1c ≥10% (≥86 mmol/mol).
• Any disease condition that may endanger subject safety or impair protocol compliance per investigator judgment.
• Subjects with inadequate standard therapy judged by investigators.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07704190 · M20260376

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗