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 2.0 dated 15-September-2025
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
Sites of Study
No of Sites = 24
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Sandeep Seth
All India Institute of Medical Sciences (AIIMS)
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 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 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
8328309714
dr.y.srinivasu@gmail.com
Dr Tom Devasia
Kasturba Hospital, an associate Hospital of MAHE
Professor and Unit Head, Department of Cardiology, Madhav Nagar, Manipal - PIN 576104.
Dakshina Kannada KARNATAKA
9448158508
tom.devasia@manipal.edu
Dr Prasad Murigendrappa Renuka
KLES Dr Prabhakar Kore Hospital & Medical Research Centre
Consultant Interventional Cardiologist, Department of Cardiology, Nehru Nagar, PIN-590010
Belgaum KARNATAKA
9243245777
drprasadmr@gmail.com
Dr Anand Kumar Valsakumar
Lakeshore Hospital and Research Centre Ltd.
Senior Consultant Interventional Cardiologist, Department of Cardiology, XVI/612, Maradu, Nettoor PO, PIN -682040, Kochi,
Ernakulam KERALA
9249488064
anandheart@gmail.com
Dr Jabir Abdullakutty
Lisie Hospital
Senior Cardiology Consultant, Department of Cardiology, P.B. No. 3053, Kochi - 682018
Ernakulam KERALA
9447011773
drjabi@yahoo.co.in
Dr Santosh Kumar Sinha
LPS Institute of Cardiology and Cardiac Surgery
Associate Professor, Department of Cardiology, G.S.V.M Medical College, G.T. Road, Swaroop Nagar, PIN- 208002,
Kanpur Nagar UTTAR PRADESH
Formulation: Tablet
Dose strength: NA
Route: Oral
Frequency: Once daily
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Type of Participant and Disease Characteristics
1 Meets one of the following:
(a) Participants with history of an ASCVD event: Participants greater than or equal to 18 years of age at the time of signing the ICF with a history of ASCVD defined as ACS within 1 to
12 months prior to randomisation, or large artery ischaemic stroke suspected to be due to atherosclerotic vascular disease within 1 to 12 months prior to randomisation, or revascularisation for symptomatic lower limb PAD, and LDL-C greater than or equal to 60 mg/dL
(greater than or equal to 1.55 mmol/L).
Additional risk factors based on the level of the screening LDL-C:
o Participants with an LDL-C greater than or equal to 60 mg/dL (greater than or equal to 1.55 mmol/L) and less than 75 mg/dL
(less than 1.9 mmol/L) must have BOTH an Lp(a) greater than or equal to 25 mg/dL (greater than or equal to 60 nmol/L) AND at least one of the other additional risk factors (i to vii) below.
o Participants with an LDL-C greater than or equal to 75 mg/dL (greater than or equal to 1.9 mmol/L) need to have at least one of the other additional risk factors (i to viii) below.
i) T2DM requiring ongoing medical therapy
ii) Age greater than or equal to 65 years
iii) Symptomatic ASCVD in at least 2 vascular beds (eg, coronary artery disease, cerebrovascular disease, or PAD)
iv) History of recurrent ASCVD events (eg, multiple ACS, ischaemic strokes, PAD events, or a combination)
v) Previous above ankle amputation due to PAD
vi) Previous diagnosis of non-end stage CKD (eGFR less than 60 mL/min/1.73 m2
vii) hs-CRP greater than or equal to 2.0 mg/L while asymptomatic and without other explanation (eg, infection)
viii) Lp(a) greater than or equal to 25 mg/dL (greater than or equal to 60 nmol/L)
(b) Participants at increased risk of a first ASCVD event: Male participant greater than or equal to 50 years of age or female participant greater than or equal to 55 years of age at the time of signing the ICF with LDL-C greater than or equal to 100 mg/dL (greater than or equal to 2.6 mmol/L) and diagnostic evidence of at least one of the following disease categories (i, ii, or iii):
i) Significant atherosclerotic artery disease with any one of the following:
a) CAC score greater than or equal to 300
b) Prior arterial revascularisation for atherosclerosis by percutaneous intervention any time prior to screening
c) Prior coronary artery bypass graft surgery greater than 5 years prior to screening
d) ABI less than or equal to 0.85
e) greater than or equal to 50% stenosis in greater than or equal to 2 coronary artery territories, or in greater than or equal to 2 vascular beds (coronary, carotid, lower extremity).
ii) High-risk Type 1 or Type 2 diabetes mellitus with manifestation of end-organ disease (diabetic nephropathy, retinopathy, neuropathy or an ABI outside the normal range [0.9 to 1.4])
iii) Documented atherosclerosis of less significance: CAC score 100 to less than 300 or not meeting criteria above in i).
For ii) and iii), participants need to have at least one of the additional risk factors (a to f) below:
a) CKD with eGFR less than or equal to 45 mL/min/1.73 m2
b) Current tobacco use
c) Age greater than or equal to 65
d) T2DM (if included on the less significant atherosclerosis criterion iii)
e) Lp(a) greater than or equal to 125 nmol/L
f) hs-CRP greater than or equal to 2.0 mg/L
2 Participant should be receiving a maximally tolerated lipid-lowering regimen including a maximally tolerated dose of a statin.
(a) Participants who are judged by the treating physician not to tolerate high-intensity statins (according to guidelines, typically, atorvastatin greater than or equal to 40 mg once daily or rosuvastatin greater than or equal to 20 mg once daily) may be included if treated with a low or moderate intensity statin dose.
(b) Participants not receiving any statins must have documented intolerable side effects to at least 2 different statins, including one at the lowest standard dose or on a chronic medication that would prohibit the use of a statin (according to the prescribing information for the statin in question).
(c) Participants must achieve a stable dose (greater than 28 days) of lipid-lowering therapies before screening.
Sex and Contraceptive/Barrier Requirements
3 Male and/or female assigned at birth, inclusive of all gender identities.
4 Female participants of childbearing potential who are sexually active with a nonsterilised male partner must be on an established highly effective form of birth control from screening throughout the study and should continue with a highly effective form of birth control for at least 10 days after the last dose of study intervention. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include:
- Systemic hormonal contraception associated with inhibition of ovulation (oral/transdermal/injectable/implantable/intravaginal)
- Intrauterine device/intrauterine hormone-releasing system
- Bilateral tubal occlusion/vasectomised partner
Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea are not acceptable methods of contraception
5 Female participants of non-childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy), or who are postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment. A high FSH level in the postmenopausal range that will depend on the normative data for the specific assay used, may also be used to confirm a postmenopausal state. At least 2 FSH levels (at least 4 weeks apart) should be within the postmenopausal range. If HRT is discontinued, the first of the 2 consecutive FSH levels should be measured at least 6 weeks from stopping HRT.
Informed Consent
1 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2 Participants must give informed consent before initiation of any study-related procedures and be willing to comply with all required study procedures
Optional Genomics Initiative Informed Consent
Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the genomic initiative.
ExclusionCriteria
Details
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1 Any underlying known disease, or condition including homozygous familial hypercholesterolaemia, or LDL or plasma apheresis within 12 months prior to randomisation, that, in the opinion of the investigator, might interfere with the interpretation of the clinical study results.
2 Any revascularisation procedure planned within the next 3 months.
3 Available imaging assessment within the last 3 years showing either coronary calcium score of zero, or a coronary computed tomography angiography with no atherosclerosis.
4 Calculated eGFR less than 15 mL/min/1.73 m2 at screening.
5 Uncontrolled severe hypertension: systolic BP greater than 160 mmHg or diastolic BP greater than 110 mmHg as measured at any screening/rescreening visits or at randomisation despite antihypertensive therapy (based on the mean of the 3 consecutive readings).
6 Severe concomitant non-CV disease with estimated life expectancy less than 2 years.
7 Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma) within the last 5 years.
1 Any laboratory values with the following deviations at screening:
- AST or ALT greater than 3 × ULN
- TBL greater than 2 × ULN (except for participants with Gilbert s syndrome where TBL 3 × ULN is acceptable provided direct bilirubin less than 1.5 × ULN)
- Fasting triglycerides greater than or equal to 400 mg/dL (greater than or equal to 4.52 mmol/L)
- Creatine kinase greater than 5 × ULN
- Urine albumin/creatinine ratio greater than or equal to 500 mg/g
2 Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
3 Known history of alcohol and/or drug abuse within the last 5 years.
4 Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal.
5 Acute ischaemic ASCVD event within 7 days prior to screening.
6 QTcF greater than 470 msec at randomisation, or with family history of long QT syndrome.
7 High-degree AV-block II-III or sinus node dysfunction with clinically significant sinus pause untreated with pacemaker.
8 Heart failure with NYHA Class IV.
9 Ventricular arrhythmia requiring treatment.
10 Previously diagnosed hypertrophic obstructive cardiomyopathy or any infiltrative cardiomyopathy such as sarcoidosis or amyloidosis.
11 Participants with a history of hypersensitivity to drugs with a similar chemical structure.
12 Any uncontrolled or serious disease, or any medical (eg, known major active infection [eg, hepatitis B and C] or major CV, haematological, renal, metabolic, gastrointestinal, respiratory, hepatic, or endocrine dysfunction) or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
13 Uncontrolled T2DM defined as HbA1c greater than or equal to 9.5% at screening.
14 Inadequately treated hypothyroidism defined as TSH greater than 1.5 × ULN at screening or participants whose thyroid replacement therapy was initiated or modified within the last 3 months prior to screening.
Prior or Planned Concomitant Therapy
15 Receiving or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation.
16 Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months of screening or planned use during the study.
17 Use of gemfibrozil within one week prior to the Screening Visit or planned use during the study.
8 Use of PCSK9 inhibitors: evolocumab/alirocumab within 12 weeks of the Screening Visit or planned use during the study, or inclisiran within 18 months of the Screening Visit or planned use during the study, or any other approved PCSK9 inhibitor use within
5 half-lives prior to the Screening Visit or planned use during the study.
Prior/Concurrent Clinical Study Experience
9 Participation in another clinical study with an IMP administered or device used within 30 days or 5 half-lives of the Screening Visit, whichever is longer.
10 Planned use of other investigational products or devices during the course of the study.
Other Exclusions
11 Any condition that could interfere with the conduct of the study as judged by the investigator, such as:
- Inability to communicate or to cooperate with the investigator.
- Inability to understand, or unlikely to comply with the protocol requirements, instructions, study-related restrictions, and the nature, scope, and possible consequences of the study
12 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
13 Previous randomisation into the present study.
Optional Genetic Sampling (Separate ICF Required)
14 Exclusion from this genetic research may be for any of the exclusion criteria specified for the main study or any of the following:
- Previous allogeneic bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.
1.1 Lifestyle Considerations
1.1.1 Meals and Dietary Restrictions
Participants must fast for at least 8 hours before each scheduled study visit. No fluids will be allowed apart from water.
Participants will be counselled to follow and adhere to a heart-healthy diet as per local or regional guidelines (eg, National Cholesterol Education Program Adult Treatment Panel III Therapeutic Lifestyle Changes diet or equivalent).
1.1.1 Caffeine, Alcohol, and Tobacco
No additional study-specific restrictions are required in the study, except restrictions applicable prior to a BP measurement or ECG measurement
1.1.2 Activity
Participants are encouraged not to start any new physical training activities or increase the intensity of their usual physical training in the 5 days prior to any study visit.
1.1.3 Other Restrictions
Participants should 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.