A Phase 3 interventional study of PCSK9 inhibitors and statins with or without ezetimibe and Statins with or without ezetimibe in Aortic Stenosis, sponsored by Beijing Anzhen Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-05-09.
Sponsored by Beijing Anzhen Hospital · Phase 3, Interventional, and Treatment
Calcific aortic stenosis (CAS) can cause severe adverse cardiac events, but there are currently no effective drugs that can prevent or delay the progression of the disease. In fact, aortic valve replacement remains the only treatment option.
CAS has been shown to be associated with Lp(a), LDL-C and PCSK9. Several observational studies indicated that the use of statins to decrease LDL-C levels was associated with the reduced incidence of CAS, but no randomized controlled trials (RCTs) showd that statins had any benefit on the progression of CAS. This may be related to the limited reduction of LDL-C by statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a new lipid-lowering drug. On the basis of statin therapy, PCSK9 inhibitors can further reduce LDL-C and Lp(a) levels by 50% to 60% and 20% to 30%, respectively. Some studies reported that elevated plasma PCSK9 levels were related to CAS and PCSK9 R46L loss-of-function mutation was associated with lower rates of CAS, and importantly, some observational studies found that PCSK9 inhibitors could reduce the incidence of CAS.
Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS. A total of 160 patients with mild or moderate CAS or asymptomatic severe AS will be randomly assigned to receive either statins or PCSK9 inhibitors+statins. All patients will be followed for at least 2 years at 3, 6,9,12,15,18,21,24 months after randomization. Quality of life (EQ-5D-3L including the EUROQOL visual analogue scale) questionnaires were gathered during each visit. Echocardiography and computer tomography were performed and blood samples were withdrawn at baseline, at 2 years visit, and before withdrawal from the study.
The primary endpoint is the average annual change in peak aortic jet velocity on echocardiography. The secondary endpoints include average annual change in aortic valve area on echocardiography, average annual change in aortic valve calcification score on cardiac non-contrast computer tomography, heart valve surgery, change in quality-of-life scores, and average annual change in aortic and coronary artery calcification. Safety endpoints include all-cause death and cardiovascular events.
The results of this trial will provide a new idea for the treatment of patients with CAS.
985 studies on the registry are indexed under Aortic Valve Stenosis; 283 are open to participants now.
This study's planned enrollment of 160 is above the median of 120 across 525 interventional studies indexed under Aortic Valve Stenosis.
Browse Aortic Valve Stenosis studies →Beijing Anzhen Hospital is the lead sponsor of 188 studies on the registry; 100 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients in experimental group are treated with PCSK9 inhibitors (140mg with Evolocumab or 75mg with Alirocumab or 150mg with Tafolecimab subcutaneously every two weeks) and conventional lipid-lowering therapy based on statins (atorvastatin 20-40mg qd with or without ezetimibe 10mg qd, or rosuvastatin 10-20mg qd with or without ezetimibe 10mg qd).
Drug: PCSK9 inhibitors and statins with or without ezetimibe
Patients in control group are only treated with conventional lipid-lowering therapy based on statins (atorvastatin 20-40mg qd with or without ezetimibe 10mg qd, or rosuvastatin 10-20mg qd with or without ezetimibe 10mg qd).
Drug: Statins with or without ezetimibe
Patients in experimental group are treated with PCSK9 inhibitors (140mg with Evolocumab or 75mg with Alirocumab or 150mg with Tafolecimab subcutaneously every two weeks) and conventional lipid-lowering therapy based on statins (atorvastatin 20-40mg qd with or without ezetimibe 10mg qd, or rosuvastatin 10-20mg qd with or without ezetimibe 10mg qd).
Also known as: Proprotein convertase subtilisin/kexin type 9 inhibitors, Hydroxymethylglutaryl-Coenzyme A Reductase inhibitors, Ezetimibe
Patients in control group are only treated with conventional lipid-lowering therapy based on statins (atorvastatin 20-40mg qd with or without ezetimibe 10mg qd, or rosuvastatin 10-20mg qd with or without ezetimibe 10mg qd).
Also known as: Hydroxymethylglutaryl-Coenzyme A Reductase inhibitors, Ezetimibe
The average annual change in peak aortic jet velocity
The peak aortic jet velocity is measured by echocardiography.
Time frame: Up to 24 months
The average annual change in aortic valve area
The aortic valve area is measured by echocardiography.
Time frame: Up to 24 months
The average annual change in aortic valve calcification score
The aortic valve calcification score is measured by cardiac noncontrast computer tomography.
Time frame: Up to 24 months
Heart valve surgery
Transcatheter aortic valve implantation or surgical aortic valve replacement
Time frame: Up to 24 months
Change in quality-of-life scores
Change in quality-of-life scores is assessed with the use of the EQ-5D-3L scale
Time frame: Up to 24 months
Safety endpoints
All-cause death or cardiovascular events
Time frame: Up to 24 months
Plan to share: No
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Beijing Anzhen Hospital