ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People Who Have Had a Heart Attack
Study Details
Study Description
Brief Summary
The research study is being done to see if ziltivekimab can be used to treat people who were admitted to hospital because of a heart attack. Ziltivekimab might reduce development of heart disease, thereby preventing new heart attacks or strokes. Participants will either get ziltivekimab (active medicine) or placebo (a dummy medicine which has no effect on the body). Which treatment participants get is decided by chance. The chance of getting ziltivekimab or placebo is the same. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe. The study will last for about 2 years.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ziltivekimab Participants will receive an initial loading dose of ziltivekimab Dose 1 subcutaneously (s.c.) as early as possible after invasive procedure, and latest within 24 hours of hospitalisation for ST-elevation myocardial infarction (STEMI) and within 48 hours of hospitalisation for non-ST-elevation myocardial infarction (NSTEMI), followed by ziltivekimab Dose 2 s.c. once-monthly during the treatment period (estimated up to 2 years) added to standard of care. |
Drug: Ziltivekimab
Ziltivekimab will be adminsitered subcutaneously as an initial loading dose of Dose 1 followed by a maintenance dose of Dose 2 once- monthly.
|
| Experimental: Placebo ziltivekimab Participants will receive placebo matched to ziltivekimab at an initial loading dose subcutaneously (s.c.) as early as possible after invasive procedure, and latest within 24 hours of hospitalisation for STEMI and latest within 48 hours of hospitalisation for NSTEMI, followed by placebo matched to ziltivekimab s.c. once-monthly during the treatment period (estimated up to 2 years) added to standard of care. |
Drug: Placebo
Placebo matched to ziltivekimab will be adminsitered subcutaneously as an initial loading dose followed by a maintenance dose once-monthly.
|
Outcome Measures
Primary Outcome Measures
- Time to first occurrence of a 3-component major adverse cardiovascular event (MACE) endpoint comprising: Cardiovascular (CV) death, Non-fatal myocardial infarction (MI), Non-fatal stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
Secondary Outcome Measures
- Number of CV death, non-fatal MI, non-fatal stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Time to first occurrence of a composite MACE endpoint consisting of: All-cause mortality, Non-fatal MI, Non-fatal stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Number of all-cause mortality, non-fatal MI, non-fatal stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Time to first occurrence of non-fatal MI [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Time to first occurrence of MI (fatal and non-fatal) [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Time to first occurrence of non-fatal stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Time to first occurrence of stroke (fatal and non-fatal) [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Time to first occurrence of a 3-component coronary MACE endpoint comprising:CV death, Non-fatal MI, Ischaemia-driven coronary revascularisation [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Time to first occurrence of a 5-component expanded MACE endpoint comprising: CV death, Non-fatal MI, Non-fatal stroke, Ischaemia-driven coronary revascularisation, Heart failure (HF) hospitalisation or urgent HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Number of CV death, non-fatal MI, non-fatal stroke, ischaemia-driven coronary revascularisation, or HF hospitalisation or urgent HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measired as count of events.
- Time to first occurrence of a 3-component HF endpoint comprising: CV death, HF hospitalisation or urgent HF visit, Outpatient HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Number of CV deaths, HF hospitalisation or urgent HF visits or outpatient HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in count of events.
- Time to first occurrence of a 2-component HF endpoint comprising: CV death, HF hospitalisation or urgent HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as months.
- Number of CV deaths, HF hospitalisation or urgent HF visits [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in count of events.
- Time to first occurrence of a 2-component expanded HF endpoint comprising: HF hospitalisation or urgent HF visit, Outpatient HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as months.
- Number of HF hospitalisation or urgent HF visit or outpatient HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Number of outpatient HF visit [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in count of events.
- Time to occurrence of CV death [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as months.
- Time to occurrence of all-cause death [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as months.
- Time to first occurrence of 6-component vascular event: CV death, Non-fatal MI, Non-fatal stroke, Ischaemia-driven coronary revascularisation, Non-coronary revascularisation, Hospitalisation for any other non-coronary ischaemic event excluding stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Number of CV death, non-fatal MI and non-fatal stroke, ischaemia-driven coronary revascularisation, non-coronary revascularisation procedure, hospitalisation for any other non-coronary ischaemic event excluding stroke [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Number of ischaemia-driven coronary revascularisation [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Time to first occurrence of ischaemia-driven coronary revascularisation or any non-coronary revascularisation [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured in months.
- Number of ischaemia-driven coronary revascularisation and any non-coronary revascularisation [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Number of cardiovascular hospitalisations [From randomisation (month 0) to 1 month/ 30 days]
Measured as count of events.
- Number of cardiovascular hospitalisations [From randomisation (month 0) to 12 months]
Measured as count of events.
- Number of hospitalisations with infection as primary cause or death due to infection [From randomisation (month 0) to end-of-study (up to 24 months)]
Measured as count of events.
- Change in high-sensitivity C-reactive protein (hs-CRP) [From randomisation (month 0) to 6 months]
Measured as ratio to baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18 years or above at the time of signing the informed consent
-
Hospitalisation for acute myocardial infarction with evidence of type 1 MI (myocardial infarction) by invasive angiography performed at site with percutaneous coronary intervention (PCI) capabilities
-
ST-segment elevation myocardial infarction (STEMI) with all the following: a) Persistent symptoms (greater than or equal to 20 min at rest) suggestive of cardiac ischaemia within 12 hours of hospitalisation (time 0), b) Electrocardiogram (ECG)-changes (in the absence of left ventricular hypertrophy or left bundle branch block): ST-segment elevation at the J point in at least two contiguous leads greater than or equal to 0.25 millivolt (mV) in men less than 40 years, greater than or equal to 0.2 mV in men greater than or equal to 40 years, or greater than or equal to 0.15 mV in women in leads V2-V3; and/or greater than or equal to 0.1 mV in all other leads OR - Non-ST-segment myocardial infarction (NSTEMI) with all the following: a) Persistent symptoms (greater than or equal to 10 minutes at rest) suggestive of cardiac ischaemia within 24 hours of hospitalisation (time 0), b) Rise and/or fall in cardiac troponin I or T with at least one value above the 99th percentile upper reference limit
-
Possibility for randomisation as early as possible after invasive procedure, and latest within 24 hours of hospitalisation for STEMI, and latest within 48 hours of hospitalisation for NSTEMI
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Presence of at least one of the following criteria: a) Any prior MI b) Prior coronary revascularisation, c) Diabetes mellitus treated with glucose-lowering agent(s), d) Known chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) greater than equal to 15 and less than 60 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2), CKD-EPI, e) Prior ischaemic stroke, f) Known carotid disease or peripheral artery disease in the lower extremities, g) Multivessel coronary artery disease (current/prior)
Exclusion Criteria:
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Use of fibrinolytic therapy for treatment of the current AMI (acute myocardial infarction)
-
Chronic heart failure classified as being in New York Heart Association (NYHA) Class IV
-
Ongoing haemodynamic instability defined as any of the following: a) Killip Class III or IV, b) Sustained and/or symptomatic hypotension (systolic blood pressure less than 90 millimeters of mercury (mmHg))
-
Severe kidney impairment defined as any of the following: a) eGFR <15 mL/min/1.73 m2 (CKD-EPI), b) Chronic haemodialysis or peritoneal dialysis
-
Known alanine aminotransferase (ALT) greater than 8 x upper limit of normal (reference range) (ULN)
-
Severe hepatic disease defined as at least one of the following: a) Previously known or current hepatic encephalopathy (clinical evaluation), b) Previously known or current ascites (clinical evaluation), c) Jaundice (clinical evaluation), d) Previous oesophageal/gastric variceal bleeding, e) Known hepatic cirrhosis
-
Major cardiac surgical (including but not restricted to coronary artery bypass graft surgery [CABG]), non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days or any major surgical procedure planned at the time of randomisation or as treatment for the current AMI (CABG). Deferred (staged) percutaneous coronary intervention for a non-culprit vessel identified during the current AMI is allowed
-
Clinical evidence of, or suspicion of, active infection at the discretion of the investigator
-
History of evidence of hepatitis such as (but not limited to): a) Known hepatitis B or hepatitis C, b) In participants with hepatitis B and C risk factors
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History or evidence of untreated latent tuberculosis (TB) such as (but not limited to): a) History of a positive TB test or chest X-ray compatible with latent TB; and TB treatment initiated less than 28 days prior to randomisation, b) Participants with TB risk factors but unwilling to undergo TB treatment if confirmed positive for latent TB based on central laboratory test at baseline (visit 2)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | New Delhi | Delhi | India | 110017 |
| 2 | Novo Nordisk Investigational Site | New Delhi | Delhi | India | 110029 |
| 3 | Novo Nordisk Investigational Site | New Delhi | Delhi | India | 110060 |
| 4 | Novo Nordisk Investigational Site | Udupi | Karnataka | India | 576104 |
| 5 | Novo Nordisk Investigational Site | Nashik | Maharashtra | India | 422005 |
| 6 | Novo Nordisk Investigational Site | Cuttack | Odisha | India | 753007 |
| 7 | Novo Nordisk Investigational Site | Hyderabad | Telangana | India | 500055 |
| 8 | Novo Nordisk Investigational Site | Kanpur | Uttar Pradesh | India | 208002 |
| 9 | Novo Nordisk Investigational Site | Lucknow | Uttar Pradesh | India | 226003 |
| 10 | Novo Nordisk Investigational Site | Lucknow | Uttar Pradesh | India | 226010 |
| 11 | Novo Nordisk Investigational Site | Lucknow | Uttar Pradesh | India | 226014 |
| 12 | Novo Nordisk Investigational Site | Dehradun | Uttarakhand | India | 248001 |
| 13 | Novo Nordisk Investigational Site | New Delhi | India |
Sponsors and Collaborators
- Novo Nordisk A/S
- Duke Clinical Research Institute
Investigators
- Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EX6018-4979
- U1111-1294-3473
- 2023-506876-28