A study on Major Adverse cardiovascular events in Patients with a History of Atherosclerotic cardiovascular disease events or at High Risk for a First Event
Scientific Title of Study
A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Effect of AZD0780 on Major Adverse Cardiovascular Events in Patients with Established Atherosclerotic Cardiovascular Disease (ASCVD) or at High Risk for a First ASCVD Event - AZURE-Outcomes
Protocol D7960C00015 Version 3.0 dated 13-March-2026
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Vijay Kumar Chopra
Designation
Senior Director,
Affiliation
Max Super Speciality Hospital Saket (East Block)
Address
(A Unit of Devki Devi Foundation)
Saket , 2, Press Enclave Road, Saket, New Delhi
New Delhi DELHI 110017 India
Phone
9650896800
Fax
Email
vijay.chopra@maxhealthcare.com
Details of Contact Person Scientific Query
Name
Tapankumar Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd,
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore.
Bangalore KARNATAKA 560045 India
Phone
9535104975
Fax
Email
Tapankumar.Shah@astrazeneca.com
Details of Contact Person Public Query
Name
Tapankumar Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd,
Address
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore.
KARNATAKA 560045 India
Phone
9535104975
Fax
Email
Tapankumar.Shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road, Bangalore - 560045, Karnataka, India
Countries of Recruitment
Argentina Brazil Bulgaria Canada Chile China Colombia Czech Republic Denmark France Germany Greece Hungary India Italy Japan Malaysia Mexico New Zealand Peru Philippines Poland Republic of Korea Romania Slovakia South Africa Spain Sweden Taiwan Thailand Turkey Ukraine United Kingdom United Republic of Tanzania Viet Nam
Professor, Department of Cardiology, Ansari Nagar, PIN - 110029
New Delhi DELHI
9650929005
drsandeepseth@hotmail.com
Dr Puneet Aggarwal
Atal Bihari Vajpayee Institute of Medical Sciences
Associate Professor, Department of Cardiology, Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, PIN - 110001
New Delhi DELHI
7235807073
puneetaggarwal4u@gmail.com
Dr Upendra Kaul
Batra Hospital and Medical Research Centre
Chairman, Department of Cardiology, 1, Tughlakabad Institutional Area, Mehrauli Badapur Road, PIN- 110062
New Delhi DELHI
9811150518
upendra.kaul@batrahospitaldelhi.org
Dr Krishnakumar P
Calicut Medical College
Department of Cardiology, Government Medical College, Kozhikode, Calicut medical College, Medical College Road, Kozhikode-673008, Kerala Kozhikode KERALA
9447658824
krishnakumarp03@gmail.com
Dr Praneeth Polamuri
Care Hospitals
Senior Conusltant, Department of Cardiology, 6-3-248/2, Road No.1, Banjara Hills, PIN- 500034
Hyderabad TELANGANA
9441490614
pran.omc@gmail.com
Dr Mohd Aziz Khan
Crescent Hospital & Heart Centre
Senior Consultant Cardiologisit, Behind Old Mount Carmel School, Near Lokmat Square, Dhantoli, PIN- 440012
Nagpur MAHARASHTRA
9823056551
khandraziz@yahoo.com
Dr Gurpreet Singh Wander
Dayanand Medical College & Hospital, Unit - Hero DMC Heart Institute
Principal and Professor, Department of Cardiology, Tagore Nagar, Civil Lines, PIN- 141001
Ludhiana PUNJAB
9815545316
drgswander@yahoo.com
Dr Sanjeev Sharma
Eternal Hearth Center
Eternal Hospital, A unit of Eternal Heart Care Centre and Research Institute, 3A, Jagatpura Road, Near Jawahar Circle Jaipur RAJASTHAN
9983333421
sanzsharma@gmail.com
Dr Peeyush Jain
Fortis Escorts Heart Institute
Director, Department of Cardiology, Okhla Road, PIN - 110025
New Delhi DELHI
9818701043
peeyush.jain@fortishealthcare.com
Dr Vimal Mehta
Govind Ballabh Pant Institute of Postgraduate Medical Education and Research
Director-Professor, Department of Cardiology, First Floor, Academic Block, Department of Cardiology, Jawahar Lal Nehru Marg, PIN- 110002
New Delhi DELHI
9718599105
drvimalmehta@yahoo.co.in
Dr Srinivasu Yalaga
Govt. Siddhartha Medical College
Assistant Professor, Department of Cardiology, Ring road, Gunadala, Vijayawada - 520008
Krishna ANDHRA PRADESH
Participants are eligible if they are adults who meet one of the following disease criteria. Participants with established atherosclerotic cardiovascular disease must have a history of myocardial infarction or ischaemic stroke due to atherosclerotic disease at least one month before randomisation, or previous revascularisation for symptomatic lower limb peripheral artery disease, and low density lipoprotein cholesterol of at least 60 milligrams per decilitre. Participants with low density lipoprotein cholesterol from 60 to less than 75 milligrams per decilitre must also have lipoprotein a of at least 50 nanomoles per litre or 25 milligrams per decilitre and at least one additional risk factor. Participants with low density lipoprotein cholesterol of at least 75 milligrams per decilitre must have at least one additional risk factor. Participants with an index myocardial infarction or stroke more than 12 months before randomisation must have polyvascular disease and, if low density lipoprotein cholesterol is between 60 and less than 75 milligrams per decilitre, lipoprotein a of at least 50 nanomoles per litre or 25 milligrams per decilitre. Additional risk factors include polyvascular disease, type 2 diabetes requiring treatment, age of at least 65 years, recurrent atherosclerotic cardiovascular disease events, previous above ankle amputation due to peripheral artery disease, non end stage chronic kidney disease with estimated glomerular filtration rate below 60 millilitres per minute per 1.73 square metres, high sensitivity C reactive protein of at least 2 milligrams per litre without another explanation, or lipoprotein a of at least 50 nanomoles per litre or 25 milligrams per decilitre. Participants at increased risk of a first atherosclerotic cardiovascular disease event must be males aged at least 50 years or females aged at least 55 years, with low density lipoprotein cholesterol of at least 100 milligrams per decilitre, no previous myocardial infarction, qualifying ischaemic stroke or symptomatic lower limb peripheral artery revascularisation, and diagnostic evidence of significant atherosclerotic disease, high risk type 1 or type 2 diabetes with end organ disease, or less significant documented atherosclerosis. Eligible disease evidence may include coronary artery calcium score of at least 100, arterial stenosis or occlusion, prior arterial revascularisation, coronary artery bypass graft surgery more than five years earlier, abnormal ankle brachial index, obstructive or polyvascular coronary disease, diabetic nephropathy, retinopathy, neuropathy or abnormal ankle brachial index, stress test evidence of coronary ischaemia, increased carotid intima media thickness, or documented atherosclerotic plaque or calcification. Participants included under high risk diabetes or less significant atherosclerosis must also have at least one additional risk factor including chronic kidney disease, current tobacco use, age of at least 65 years, type 2 diabetes, elevated lipoprotein a or high sensitivity C reactive protein. All participants must receive stable background lipid lowering treatment for more than 28 days, expected to reduce low density lipoprotein cholesterol by approximately 50 percent, consisting of a high intensity statin, a lower intensity statin with ezetimibe or bempedoic acid, or the maximum tolerated statin regimen with oral combination therapy strongly recommended. All participants must be assigned male or female at birth, be capable of providing informed consent, provide written informed consent before study procedures and comply with study requirements. Females of childbearing potential must use highly effective contraception together with a barrier method from screening until at least 10 days after the last dose of study treatment. Females of non childbearing potential must be permanently sterilised or postmenopausal as defined by the protocol. Optional genomics participation requires separate written informed consent before sample collection.
ExclusionCriteria
Details
Participants will be excluded if they have any disease or condition that may interfere with study assessments, including homozygous familial hypercholesterolaemia, plasma or low density lipoprotein apheresis within 12 months before randomisation, planned revascularisation within three months, recent imaging showing a coronary calcium score of zero or no coronary atherosclerosis, estimated glomerular filtration rate below 15 millilitres per minute per 1.73 square metres, uncontrolled severe hypertension with systolic blood pressure above 160 millimetres of mercury or diastolic blood pressure above 110 millimetres of mercury, severe non cardiovascular disease with life expectancy below two years, malignancy within the previous three years except non melanoma skin cancer or cervical carcinoma in situ, or major organ transplantation. Participants will also be excluded for clinically significant laboratory abnormalities, including aspartate aminotransferase or alanine aminotransferase above three times the upper limit of normal, total bilirubin above two times the upper limit of normal, fasting triglycerides of at least 400 milligrams per decilitre, creatine kinase above five times the upper limit of normal, or urine albumin to creatinine ratio of at least 500 milligrams per gram. Other exclusions include pregnancy, breastfeeding, alcohol or drug abuse within the previous five years, hypersensitivity or previous intolerance to AZD0780, uncontrolled or serious medical or surgical conditions, uncontrolled type 2 diabetes with glycated haemoglobin of at least 9.5 percent, and inadequately treated hypothyroidism. Participants must not have used mipomersen or lomitapide within 12 months before screening, gemfibrozil within one week before screening, or PCSK9 inhibitors within the protocol specified washout periods, and must not plan to use these treatments during the study. Participants will be excluded if they have participated in specified AZD0780 studies or another clinical study involving an investigational product or device within 30 days or five half lives before screening, whichever is longer, or if they plan to use another investigational product or device during the study. Additional exclusions include inability to communicate or cooperate with the investigator, inability or unwillingness to understand or comply with study requirements, involvement in study planning or conduct, previous randomisation in the current study, an acute ischaemic atherosclerotic cardiovascular disease event within seven days before randomisation, corrected QT interval using Fridericia correction above 500 milliseconds without an alternative explanation, or sustained spontaneous ventricular arrhythmia requiring treatment within 30 days before randomisation without an implantable cardioverter defibrillator. Participants undergoing optional genetic research will also be excluded if they have received an allogeneic bone marrow transplant or a non leukocyte depleted whole blood transfusion within 120 days before genetic sample collection. Participants must fast for at least eight hours before scheduled study visits and consume only water during the fasting period, follow a heart healthy diet according to local guidelines, avoid starting new physical training or increasing usual training intensity during the five days before study visits, and refrain from blood donation throughout the study.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MACE-PLUS (the composite of CV death, MI, ischaemic stroke, acute lower limb ischemia, major amputation of a vascular aetiology, and urgent arterial revascularisation)
Time to first event of any component of MACE-PLUS
Secondary Outcome
Outcome
TimePoints
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of 3P-MACE (the composite of CV death, MI, and ischaemic stroke)
Time to first event of any component of 3P-MACE
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MACE-PLUS in patients with a history of ASCVD
Time to first event of any component of MACE-PLUS
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MI
Time to first event of MI
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of urgent coronary revascularisation
Time to first event of urgent coronary revascularisation
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of CV death
Time to CV death
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MALE (the composite of acute lower limb ischemia, major amputation of vascular aetiology, and urgent lower extremity revascularisation)
Time to first event of MALE
To compare the effect of treatment with AZD0780 to placebo in reducing the risk of all-cause mortality
Time to all-cause mortality
Target Sample Size
Total Sample Size="15100" Sample Size from India="600" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
20/10/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
04/06/2025
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="5" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is designed to assess the effect of AZD0780 compared with placebo in reducing the risk of MACE-PLUS in participants with established ASCVD or those at high risk for a first ASCVD event.
ASCVD is one of the leading causes of death, causing 18.6 million deaths globally in 2019 (Pirillo et al 2021). Dyslipidaemia (ie, hyperlipidaemia, or elevated LDL-C) is one of the main causal factors of ASCVD and the main interventional target for preventing ASCVD (Ferenceet al 2018, Pirillo et al 2021, Roth et al 2020).
Dyslipidaemia is treated mainly with statins, ezetimibe, bempedoic acid, and parenteral PCSK9 inhibitors, where statins are the first-line therapy for lowering of LDL-C (Grundy et al2019, Mach et al 2020). Observational data sets correlating LDL-C levels with the incidence of CV events, as well as several landmark statin clinical studies, have demonstrated a proportional and linear relationship between LDL-C and CV events (Ference et al 2017, Schubert et al 2021). Secondary outcome studies also demonstrated that incremental LDL-C reduction derived from maximal statin therapy is associated with both a clinical and statistically significant benefit in CV events such as composite endpoints of the aggregate of death, MI, stroke, coronary revascularisation, and hospitalisation for unstable angina (Cannonet al 2004, Pedersen et al 2005, Waters et al 2006, Collins et al 2016). A meta-analysis of more than 170,000 participants in 26 randomised, controlled studies of statins has shown that “further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1.0 mmol/L reduction reducing the annual rate of these major vascular events by just over 20%. There was no evidence of any threshold within the cholesterol range studied” (Borén et al 2020, Cholesterol Treatment Trialists’ Collaboration et al 2010, Ference et al 2017).
Current guidelines call for LDL-C to be lowered with maximally tolerated statins in patients at high risk or with existing ASCVD. However, despite many available LDL-C lowering agents, many patients still do not reach the recommended LDL-C target levels and remain at increased risk of CV morbidity/mortality.
PCSK9 is an enzyme promoting degradation of the LDL receptor. The reduction of circulating PCSK9 increases LDL receptor levels and lowers plasma LDL-C. Subcutaneously injected drugs targeting PCSK9 (evolocumab and alirocumab [monoclonal antibodies], and inclisiran [silencing RNA]) have been approved for the treatment of patients at high CV risk and residual dyslipidaemia, but oral PCSK9 inhibitors are not yet available. AZD0780 is a small-molecule PCSK9 inhibitor that may provide an effective and simple orally administered new treatment option for secondary prevention in patients with established ACSVD and primary prevention in those at high risk for a first ASCVD event who are not reaching treatment goals with current therapies.