Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer

Cancer Clinical Trial

Official title:

Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05976893
• Other study ID #: PICVDAC
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: August 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Xinjiang Medical University
• Contact: Xiang Xie, PhD
• Phone: +869914366892
• Email: xiangxie999[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a prospective, randomized, open-label, and single center trial. To evaluate the effect of treatment with PCSK9 inhibitor on the risk for cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, or coronary revascularization in patients with very high risk of atherosclerotic cardiovascular disease (ASCVD) and cancer.

Description:

Subjects will be randomly assigned in a 1:1 ratio to receive subcutaneous injections of PCSK9 inhibitor (evolocumab:420 mg every 4 weeks) plus moderate intensity statin therapy or the statin alone therapy. After randomization, patients will come to the hospital every 4 weeks to collect relevant laboratory results and clinical outcomes, and be detected by echocardiography and carotid ultrasound every 12 weeks until the end of follow-up at week 48 or the occurrence of an endpoint event. The entire study is expected to be conducted for 3 years, with a recruitment period of 2 years.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 620
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male or female = 18 to = 80 years of age

• Patients with very high risk of ASCVD (with any of the following):

1. Documented ASCVD, either clinical or unequivocal on imaging. Documented ASCVD includes previous acute coronary syndrome (ACS), stable angina, coronary revascularization (percutaneous coronary intervention, coronary artery bypass graft, and other arterial revascularization procedures), stroke and transient ischemic attack (TIA), and peripheral arterial disease. Unequivocally documented ASCVD on imaging includes those findings that are known to be predictive of clinical events, such as significant plaque on coronary angiography or computed tomography (CT) scan (multivessel coronary disease with two major epicardial arteries having >50% stenosis), or on carotid ultrasound.

2. Diabetes mellitus (DM) with target organ damage, or at least three major risk factors, or early onset of type 1 diabetes mellitus (T1DM) of long duration (>20 years).

• Patients have been diagnosed with cancer through histopathology and have a life expectancy of more than 1 year

• Fasting low-density lipoprotein cholesterol (LDL-C) = 1.8 mmol/L or non-high-density lipoprotein cholesterol (non HDL-C) > 2.6 mmol/L

• Participate voluntarily and sign an informed consent

• Negative serum Pregnancy test (in women with fertility potential)

Exclusion Criteria:

• Pregnant and lactating women

• During the study period and within 3 months of receiving the last dose of the study drug, women with fertility intentions and men unwilling to use effective contraceptive methods

• New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction < 30%

• Uncontrolled hypertension, defined as systolic blood pressure = 180 mmHg and/or diastolic blood pressure = 110 mmHg

• Plan for coronary revascularization or other cardiac surgery in recent (within 3 months after randomization)

• Severe renal insufficiency, defined as estimated glomerular filtration rate (eGRF) < 30ml/min/1.73m2 or Serum creatinine (Scr) > 221 umol/L

• Severe liver dysfunction, defined as an increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3 times above the upper limit of normal

• Have used PCSK9 inhibitors within 3 months before enrollment, or have a history of severe allergic reactions to PCSK9 inhibitors

• Severe infections requiring intravenous antibiotics

• HIV-positive or history of acquired immunodeficiency syndrome (AIDS)

• With cognitive impairment or psychiatric illnesses

• Participating in other trials

Related Conditions & MeSH terms

• ASCVD
• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cancer
• Cardiovascular Diseases
• Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor

Intervention

Drug:
• Evolocumab
Evolocuma:420 mg every 4 weeks
• Statin
The moderate intensity statins used during the study are one of atorvastatin 10-20mg qd, resuvastatin 5-10mg qd, and xuezhikang 0.6g bid (statin intolerance).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Xiang Xie	Xinjiang Medical University

References & Publications (24)

American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S144-S174. doi: 10.2337/dc22-S010. Erratum In: Diabetes Care. — View Citation

Atherosclerosis and Coronary Heart Disease Working Group of Chinese Society of Cardiology; Editorial Board of Chinese Journal of Cardiology. [Chinese expert consensus on lipid management of very high-risk atherosclerotic cardiovascular disease patients]. — View Citation

Bergom C, Bradley JA, Ng AK, Samson P, Robinson C, Lopez-Mattei J, Mitchell JD. Past, Present, and Future of Radiation-Induced Cardiotoxicity: Refinements in Targeting, Surveillance, and Risk Stratification. JACC CardioOncol. 2021 Sep 21;3(3):343-359. doi — View Citation

Bharadwaj A, Potts J, Mohamed MO, Parwani P, Swamy P, Lopez-Mattei JC, Rashid M, Kwok CS, Fischman DL, Vassiliou VS, Freeman P, Michos ED, Mamas MA. Acute myocardial infarction treatments and outcomes in 6.5 million patients with a current or historical d — View Citation

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Inves — View Citation

China Cholesterol Education Program (CCEP) Working Committee; Atherosclerosis Thrombosis Prevention and Control Subcommittee of Chinese International Exchange and Promotion Association for Medical and Healthcare; Cardiovascular Disease Subcommittee of Chi — View Citation

Desai NR, Giugliano RP, Zhou J, Kohli P, Somaratne R, Hoffman E, Liu T, Scott R, Wasserman SM, Sabatine MS. AMG 145, a monoclonal antibody against PCSK9, facilitates achievement of national cholesterol education program-adult treatment panel III low-densi — View Citation

Gevaert SA, Halvorsen S, Sinnaeve PR, Sambola A, Gulati G, Lancellotti P, Van Der Meer P, Lyon AR, Farmakis D, Lee G, Boriani G, Wechalekar A, Okines A, Asteggiano R. Evaluation and management of cancer patients presenting with acute cardiovascular diseas — View Citation

Gong Y, Li X, Ma X, Yu H, Li Y, Chen J, Zhang G, Wang B, Qi X, Meng H, Wang X, Mu J, Hu X, Wang J, Liu S, Liu G, Yang Z, Zhou Y, Kong X, Yan Y, Wang C, Wang JA, Wang L, Fu G, Wei L, Peng D, Zhang S, Li R, Mao A, Bian R, Tang W, Ran Y, Jiang J, Huo Y. Lipi — View Citation

Hao Q, Aertgeerts B, Guyatt G, Bekkering GE, Vandvik PO, Khan SU, Rodondi N, Jackson R, Reny JL, Al Ansary L, Van Driel M, Assendelft WJJ, Agoritsas T, Spencer F, Siemieniuk RAC, Lytvyn L, Heen AF, Zhao Q, Riaz IB, Ramaekers D, Okwen PM, Zhu Y, Dawson A, — View Citation

Hu J, La Vecchia C, de Groh M, Negri E, Morrison H, Mery L; Canadian Cancer Registries Epidemiology Research Group. Dietary cholesterol intake and cancer. Ann Oncol. 2012 Feb;23(2):491-500. doi: 10.1093/annonc/mdr155. Epub 2011 May 4. — View Citation

In China TWCOTROCHAD, Hu SS. Report on cardiovascular health and diseases in China 2021: an updated summary. J Geriatr Cardiol. 2023 Jun 28;20(6):399-430. doi: 10.26599/1671-5411.2023.06.001. — View Citation

Integrative Cardio-Oncology Society of China Anti-Cancer Association. [Chinese expert consensus on lipid management in patients with malignancy]. Zhonghua Zhong Liu Za Zhi. 2021 Oct 23;43(10):1043-1053. doi: 10.3760/cma.j.cn112152-20210415-00321. Chinese. — View Citation

Lyon AR, Lopez-Fernandez T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, Boriani G, Cardinale D, Cordoba R, Cosyns B, Cutter DJ, de Azambuja E, de Boer RA, Dent SF, Farmakis D, Gevaert SA, Gorog DA, Herrmann J, Lenihan D, Moslehi J, Moura B, Salinge — View Citation

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ES — View Citation

Miller KD, Nogueira L, Devasia T, Mariotto AB, Yabroff KR, Jemal A, Kramer J, Siegel RL. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin. 2022 Sep;72(5):409-436. doi: 10.3322/caac.21731. Epub 2022 Jun 23. — View Citation

O'Donoghue ML, Giugliano RP, Wiviott SD, Atar D, Keech A, Kuder JF, Im K, Murphy SA, Flores-Arredondo JH, Lopez JAG, Elliott-Davey M, Wang B, Monsalvo ML, Abbasi S, Sabatine MS. Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascu — View Citation

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. — View Citation

Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA; Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety — View Citation

Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. — View Citation

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM; ODYSSEY OUTC — View Citation

Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108. — View Citation

Zeng H, Chen W, Zheng R, Zhang S, Ji JS, Zou X, Xia C, Sun K, Yang Z, Li H, Wang N, Han R, Liu S, Li H, Mu H, He Y, Xu Y, Fu Z, Zhou Y, Jiang J, Yang Y, Chen J, Wei K, Fan D, Wang J, Fu F, Zhao D, Song G, Chen J, Jiang C, Zhou X, Gu X, Jin F, Li Q, Li Y, — View Citation

Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Lia — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major cardiovascular adverse events	Major cardiovascular adverse events include cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, and coronary revascularization	From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
Secondary	All cause death	All cause death	From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
Secondary	Composite end points	Composite end points include cardiogenic shock, cardiac arrest, malignant arrhythmia, heart failure, Non-coronary revascularization	From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
Secondary	The compliance rate of lipid control	Main indicator: LDL-C decreased to below 1.4 mmol/L and decreased by more than 50% from baseline; secondary indicator: non HDL-C<2.2 mmol/L;	From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
Secondary	The changes of carotid plaque	By carotid ultrasound	From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks