Aortic Stenosis, CalcificPhase 3PICASONCT07256197
PCSK9 Inhibitors in the Treatment of Calcific Aortic Stenosis
A Phase 3 study testing Treatment with PCSK9 inhibitors and Treatment without PCSK9 inhibitors in people with Aortic Stenosis, Calcific, run by Beijing Anzhen Hospital at 1 site in China.
Trial summary
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. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Aortic Stenosis, Calcific
- What is being tested?
- Treatment with PCSK9 inhibitors and Treatment without PCSK9 inhibitors
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2026to 31 Jan 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-85 years old, clinically diagnosed with mild or moderate CAVS (echocardiography shows ejection fraction > 50%; valve orifice area > 1.0 cm²; left ventricular stroke volume index > 35 ml/m²; flow velocity ≥ 2 m/s and < 4 m/s, or mean transvalvular pressure gradient < 40 mmHg) and currently not requiring valve replacement therapy;
- LDL-C ≥ 2.6 and < 4.9 mmol/L, or Lp(a) ≥ 30 mg/dL, or receiving statin therapy due to a clinical diagnosis of hypercholesterolemia/hyperlipidemia;
- Patients who can understand the purpose of the trial, voluntarily participate, sign the informed consent form, and are willing to undergo clinical follow-up in accordance with the trial requirements.
- The position and method of measurement have been further clarified in ultrasonic measurement to ensure comparability among all enrolled patients, as follows: Aortic valve peak flow velocity, aortic valve mean pressure gradient, and valve orifice area (select images of at least 3 consecutive cardiac cycles with stable heart rate; for atrial fibrillation, select images of more than 5 consecutive cardiac cycles; obtain the peak blood flow velocity of the aortic valve orifice using continuous wave Doppler in the apical 5-chamber view; calculate the instantaneous aortic valve pressure gradient using the simplified Bernoulli equation, and calculate the standardized aortic valve orifice area using the continuity equation; all participating sonographers will receive unified training, perform measurements in fixed views and retain images, which will then be reviewed by two experienced sonographers who are blinded to the trial in the core laboratory).
Who cannot join
- Any previous treatment with PCSK9 inhibitors;
- Patients must be treated with PCSK9 inhibitors by physician's judgment;
- Patients who cannot maintain PCSK9 inhibitor use for 24 months;
- Contraindications or hypersensitivity to PCSK9 inhibitors;
- Suspected or confirmed familial hypercholesterolemia;
- Fasting triglycerides (TG) >400 mg/dL (4.5 mmol/L) at baseline screening;
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- Thyroid hypofunction;
- Active or chronic liver disease;
- Severe renal insufficiency (eGFR <30 mL/min/1.73 m²);
- History of intracranial hemorrhage;
- History of alcohol or drug abuse；
- Known active infection, or severe hematologic, metabolic, or endocrine dysfunction;
- Systemic corticosteroid or cyclosporine therapy within the past 3 months;
- Active malignancy;
- Any life-threatening condition with life expectancy less than 12 months;
- Rheumatic aortic stenosis;
- Severe mitral stenosis (mitral valve area <1 cm²);
- Severe mitral or aortic regurgitation;
- Planned cardiac valve surgery;
- Left ventricular ejection fraction < 30% or severe heart failure (NYHA class III or IV);
- Implanted permanent pacemaker or cardioverter-defibrillator;
- Drug-refractory arrhythmias;
- Pregnancy, lactation, or planned pregnancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Anzhen Hospital, Capital Medical University
Beijing, Beijing Municipality, 100029
Xiaoteng Ma, +8618810616459, maxiaotengai@163.com
Zhijian Wang
About this study
Official title: Effect and Safety of PCSK9 Inhibitors on the Progression of Mild/Middle Calcific Aortic Stenosis: A Randomized Controlled Clinical Trial
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. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS.
Read the detailed description
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 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 not currently requiring valve replacement therapy will be enrolled and randomized (stratified by center) in a 1:1 ratio to two groups, the PCSK9 inhibitor treatment group (test group) or the no PCSK9 inhibitor group (control group). All patients will be followed for at least 2 years after randomization. After enrollment, telephone follow-ups will be conducted in the first month and every three months to collect data including medication use, quality-of-life scores, and clinical endpoint events. Doppler echocardiography will be collected at baseline, the 1-year visit, the 2-year visit, and before study withdrawal. Blood samples and aortic computed tomography angiography (CTA) will be collected at baseline, the 2-year visit, and before study withdrawal. The primary endpoint is the annualized mean change in peak aortic jet velocity over the 24-month follow-up period. Secondary endpoints include the annualized mean change in aortic valve area by echocardiography, the annualized mean change in aortic valve calcium score by aortic CTA, the incidence of cardiac valve surgery, and changes in quality-of-life scores. The safety endpoint is a composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. The results of this trial will provide new insights into the treatment of CAS patients.
Blood samples should be tested for serological indicators, including blood routine, C-reactive protein (CRP), biochemical, coagulation function, brain natriuretic peptide (BNP), markers of myocardial injury, glycosylated hemoglobin, erythrocyte sedimentation rate, cytokines (12 items).
- Conditions
- Aortic Stenosis, Calcific
- Being tested
- Treatment with PCSK9 inhibitors, Treatment without PCSK9 inhibitors
- Keywords
- PCSK9 Inhibitors, Calcific Aortic Stenosis
- Medical subject headings
- Aortic Valve, Calcification of
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with PCSK9 inhibitorsDrug
Also called Treatment with Proprotein convertase subtilisin/kexin type 9 inhibitors
Patients in experimental group are treated with PCSK9 inhibitors (Tafolecimab subcutaneously every two weeks) plus guideline-directed management in cardiovascular primary or secondary prevention.
Treatment without PCSK9 inhibitorsOther
Also called Treatment without Proprotein convertase subtilisin/kexin type 9 inhibitors
Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with PCSK9 inhibitors | Experimental | Patients in experimental group are treated with PCSK9 inhibitors (150mg Tafolecimab subcutaneously every two weeks) and guideline-directed management in cardiovascular primary or secondary prevention. Receives: Drug: Treatment with PCSK9 inhibitors |
| Treatment without PCSK9 inhibitors | Other | Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment. Receives: Other: Treatment without PCSK9 inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
The annualized mean change in peak aortic jet velocity
The peak aortic jet velocity is measured by echocardiography.
Measured: Up to 24 months
Secondary outcomes (4)
The annualized mean change in aortic valve area
The aortic valve area is measured by echocardiography.
Measured: Up to 24 months
The annualized mean change in aortic valve calcium score
The aortic valve calcification score is measured by aortic computed tomography angiography.
Measured: Up to 24 months
Cardiac valve surgery
Transcatheter aortic valve implantation or surgical aortic valve replacement
Measured: 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
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2025
- Study start1 Apr 2026 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Aortic Stenosis, CalcificStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Anzhen Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Jishuitan Hospital, Chinese Academy of Medical Sciences, Fuwai Hospital, Beijing Hospital, Nanchong Central Hospital, Peking University First Hospital, Beijing Luhe Hospital
- Responsible party
- Principal investigator, Zhi Jian Wang, Beijing Anzhen Hospital
- Investigators
- Zhijian Wang, Study chair, Beijing Anzhen HospitalXiaoteng Ma, Principal investigator, Beijing Anzhen Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07256197
- Sponsor's protocol ID
- PICASO
- Acronym
- PICASO
- Status last verified
- Dec 2025
- First submitted
- 20 Nov 2025
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Leopold JA. PCSK9 and Calcific Aortic Valve Stenosis: Moving Beyond Lipids. JACC Basic Transl Sci. 2020 Jul 27;5(7):662-664. doi: 10.1016/j.jacbts.2020.06.004. eCollection 2020 Jul.
PubMed 32760918O'Donoghue ML, Fazio S, Giugliano RP, Stroes ESG, Kanevsky E, Gouni-Berthold I, Im K, Lira Pineda A, Wasserman SM, Ceska R, Ezhov MV, Jukema JW, Jensen HK, Tokgozoglu SL, Mach F, Huber K, Sever PS, Keech AC, Pedersen TR, Sabatine MS. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk. Circulation. 2019 Mar 19;139(12):1483-1492. doi: 10.1161/CIRCULATIONAHA.118.037184.
PubMed 30586750Langsted A, Nordestgaard BG, Benn M, Tybjaerg-Hansen A, Kamstrup PR. PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis. J Clin Endocrinol Metab. 2016 Sep;101(9):3281-7. doi: 10.1210/jc.2016-1206. Epub 2016 May 24.
PubMed 27218270Mateos N, Gomez M, Homar A, Garcia-Elias A, Yanez L, Tajes M, Molina L, Ble M, Cladellas M, Roqueta C, Benito B. Plasmatic PCSK9 Levels Are Associated with Very Fast Progression of Asymptomatic Degenerative Aortic Stenosis. J Cardiovasc Transl Res. 2022 Feb;15(1):5-14. doi: 10.1007/s12265-021-10138-4. Epub 2021 Aug 2.
PubMed 34341879Poggio P, Songia P, Cavallotti L, Barbieri SS, Zanotti I, Arsenault BJ, Valerio V, Ferri N, Capoulade R, Camera M. PCSK9 Involvement in Aortic Valve Calcification. J Am Coll Cardiol. 2018 Dec 18;72(24):3225-3227. doi: 10.1016/j.jacc.2018.09.063. No abstract available.
PubMed 30545459Raal FJ, Giugliano RP, Sabatine MS, Koren MJ, Langslet G, Bays H, Blom D, Eriksson M, Dent R, Wasserman SM, Huang F, Xue A, Albizem M, Scott R, Stein EA. Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials. J Am Coll Cardiol. 2014 Apr 8;63(13):1278-1288. doi: 10.1016/j.jacc.2014.01.006. Epub 2014 Feb 5.
PubMed 24509273Bergmark BA, O'Donoghue ML, Murphy SA, Kuder JF, Ezhov MV, Ceska R, Gouni-Berthold I, Jensen HK, Tokgozoglu SL, Mach F, Huber K, Gaciong Z, Lewis BS, Schiele F, Jukema JW, Pedersen TR, Giugliano RP, Sabatine MS. An Exploratory Analysis of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition and Aortic Stenosis in the FOURIER Trial. JAMA Cardiol. 2020 Jun 1;5(6):709-713. doi: 10.1001/jamacardio.2020.0728.
PubMed 32347887Capoulade R, Yeang C, Chan KL, Pibarot P, Tsimikas S. Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2018 Dec 1;3(12):1212-1217. doi: 10.1001/jamacardio.2018.3798.
PubMed 30476957Capoulade R, Chan KL, Yeang C, Mathieu P, Bosse Y, Dumesnil JG, Tam JW, Teo KK, Mahmut A, Yang X, Witztum JL, Arsenault BJ, Despres JP, Pibarot P, Tsimikas S. Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. J Am Coll Cardiol. 2015 Sep 15;66(11):1236-1246. doi: 10.1016/j.jacc.2015.07.020.
PubMed 26361154Zheng KH, Tsimikas S, Pawade T, Kroon J, Jenkins WSA, Doris MK, White AC, Timmers NKLM, Hjortnaes J, Rogers MA, Aikawa E, Arsenault BJ, Witztum JL, Newby DE, Koschinsky ML, Fayad ZA, Stroes ESG, Boekholdt SM, Dweck MR. Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis. J Am Coll Cardiol. 2019 May 7;73(17):2150-2162. doi: 10.1016/j.jacc.2019.01.070.
PubMed 31047003Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O'Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kalsch H, Muhleisen TW, Nothen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O'Donnell CJ, Post WS; CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013 Feb 7;368(6):503-12. doi: 10.1056/NEJMoa1109034.
PubMed 23388002Perrot N, Valerio V, Moschetta D, Boekholdt SM, Dina C, Chen HY, Abner E, Martinsson A, Manikpurage HD, Rigade S, Capoulade R, Mass E, Clavel MA, Le Tourneau T, Messika-Zeitoun D, Wareham NJ, Engert JC, Polvani G, Pibarot P, Esko T, Smith JG, Mathieu P, Thanassoulis G, Schott JJ, Bosse Y, Camera M, Theriault S, Poggio P, Arsenault BJ. Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis. JACC Basic Transl Sci. 2020 Jul 1;5(7):649-661. doi: 10.1016/j.jacbts.2020.05.004. eCollection 2020 Jul.
PubMed 32760854Guddeti RR, Patil S, Ahmed A, Sharma A, Aboeata A, Lavie CJ, Alla VM. Lipoprotein(a) and calcific aortic valve stenosis: A systematic review. Prog Cardiovasc Dis. 2020 Jul-Aug;63(4):496-502. doi: 10.1016/j.pcad.2020.06.002. Epub 2020 Jun 8.
PubMed 32526213Youssef A, Clark JR, Koschinsky ML, Boffa MB. Lipoprotein(a): Expanding our knowledge of aortic valve narrowing. Trends Cardiovasc Med. 2021 Jul;31(5):305-311. doi: 10.1016/j.tcm.2020.06.001. Epub 2020 Jun 7.
PubMed 32525013Capoulade R, Cariou B. Editorial commentary: Lp(a) and calcific aortic valve stenosis: Direct LPA targeting or PCSK9-Lowering therapy? Trends Cardiovasc Med. 2021 Jul;31(5):312-314. doi: 10.1016/j.tcm.2020.06.009. Epub 2020 Jul 2. No abstract available.
PubMed 32623063