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AZURE-Outcomes Trial
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
- Lay language title: A Trial to Test How AZD0780 Affects Serious Heart, Stroke, or Vascular Problems in Patients with Heart, Stroke or Vascular Disease or at High Risk for Such Issues
- EU trial number: 2025-520519-14
Trial background:
Researchers are looking for a better way to prevent atherosclerotic cardiovascular disease. Atherosclerotic Cardiovascular Disease (ASCVD) refers to a group of conditions that affect the heart and blood vessels. ASCVD can be caused by a buildup of fatty deposits in the arteries. These fatty deposits are called plaque.
Low-density lipoprotein (LDL) cholesterol, often known as “bad cholesterol”, is one of the biggest causes of plaque buildup. Over time, plaque can narrow or block blood vessels, limiting blood flow to important organs and the limbs. This increases the risk of ASCVD events such as heart attack and stroke. There are several current treatments that can help to lower LDL cholesterol and reduce the risk of heart disease. But, these treatments do not work well enough for everyone, and many people continue to have a high risk for ASCVD events.
MACE-PLUS is an umbrella term for serious health problems caused by blocked or narrowed blood vessels. It stands for “major adverse cardiovascular events” and other severe blood vessel problems. MACE-PLUS events include heart attack, stroke, severe blood flow issues in the legs, and death due to heart or blood vessel-related problems. MACE-PLUS also includes medical procedures needed to treat these problems, such as removal of a body part (amputation) or surgeries to improve blood flow.
The trial drug AZD0780 is designed to help reduce the levels of LDL cholesterol in the blood by blocking a protein called PCSK9. Researchers think that by lowering cholesterol, AZD0780 could help prevent MACE-PLUS in adults who have ASCVD or who are at risk for an ASCVD event.
In this trial, researchers want to learn more about the safety of AZD0780 and how well it works to prevent MACE-PLUS when compared to a placebo. A placebo looks like AZD0780 but does not have any medicine in it.
Primary objectives
Does AZD0780 help participants go longer without experiencing MACE-PLUS compared to a placebo?
Endpoints: Researchers will keep track of how long the participants are in the trial without having any of the conditions related to MACE-PLUS. Then, researchers will compare the results between the group taking AZD0780 and the group taking the placebo.
Secondary objectives
Does AZD0780 help participants go longer without having a heart attack, stroke, or dying from heart or blood vessel-related problems compared to a placebo?
Endpoints: Researchers will keep track of how long the participants are in the trial without having a heart attack, stroke, or dying from heart or blood vessel-related problems. Then, they will compare the results between groups.
Does AZD0780 help participants who have a history of ASCVD go longer without experiencing MACEPLUS compared to a placebo?
Endpoints: Researchers will keep track of how long the participants with a history of ASCVD are in the trial without having any of the conditions related to MACEPLUS. Then, researchers will compare the results between the group taking AZD0780 and the group taking the placebo.
Does AZD0780 help participants go longer without having a heart attack?
Endpoints: Researchers will keep track of how long the participants are in the trial without having a heart attack.
Does AZD0780 help participants go longer without needing an emergency procedure or surgery to improve blood flow when the heart arteries are clogged?
Endpoints: Researchers will keep track of how long the participants are in the trial without needing an emergency procedure/surgery to improve blood flow to the heart arteries.
Does AZD0780 help participants go longer without dying from heart or blood vessel-related problems compared to a placebo?
Endpoints: Researchers will keep track of how long the participants are in the trial without dying from heart or blood vessel problems. Then, they will compare the results between groups.
Does AZD0780 help participants go longer without having serious blood flow issues in their legs, or needing amputation or other surgery due to blood flow issues, compared to a placebo?
Endpoints: Researchers will keep track of how long the participants are in the trial without having serious blood flow issues in their legs or needing amputation or other surgery due to blood flow issues. Then, they will compare the results between groups.
Does AZD0780 help participants live longer compared to a placebo?
Endpoints: Researchers will keep track of how long the participants live during the trial after starting treatment. Then, they will compare the results between groups.
How does the overall health of the participants change during the trial?
Endpoints: Researchers will keep track of any medical problems (adverse events) that happen during the trial. They will also look at the results of different tests and measurements to see if there are any changes to the participants’ health after starting trial treatment.
Trial design:
This is a Phase 3, randomized, double-blind, placebo-controlled trial. Randomized means that a computer program will randomly assign the treatment each participant takes. Double-blind means none of the participants; researchers, trial doctors, or other trial staff will know what treatment each participant takes. Placebo-controlled means that some participants will take a placebo. The participants will continue receiving trial treatment until they complete the trial, they choose to leave the trial, or the researchers decide to end the treatment.
Trial population:
This trial will include up to about 15,100 participants. To join this trial, people must be at least 18 years old and have a history of an ASCVD event or be 50 years old (males) or 55 years old (females) and be at high risk for a first ASCVD event. They should not have had any other serious medical conditions that would make it too risky for them to join. Participants will already be taking at least 1 other medication if appropriate, such as a statin, to help lower their cholesterol levels.
Treatments and procedures:
The trial will begin with a 21-day screening period when the trial doctors will look at the participants’ health and do certain tests to make sure they are eligible to participate in the trial. The participants will then be randomly assigned to one of the 2 groups in the table below. While the participants are taking treatment, they will visit the trial site about 7 times during the first year. After the first year, the participants will continue visiting the trial site every 26 weeks for as long as they are in the trial. A final visit will take place after the last treatment dose. The length of time the participants are in the trial may vary, depending on when they joined the trial.
Group 1
- About 7,550 participants
- Drug: AZD0780
- Taken as tablets by mouth, once a day
Group 2
- About 7,550 participants
- Drug: Placebo
- Taken as tablets by mouth, once a day
To monitor the participants’ health throughout the trial, the doctors will do the following:
- Test the participants’ blood and urine
- Perform physical exams
- Check the participants’ vital signs
- Test the participants’ heart function using an electrocardiogram (ECG)
- Ask about the participants’ medications and any medical problems
Ethical considerations:
All participants will help researchers learn more about how AZD0780 works for preventing MACE-PLUS.
A possible benefit for taking AZD0780 is preventing MACE-PLUS. Some possible risks for taking AZD0780 are below:
- Increase in blood pressure
- Vomiting
- Difficulty breathing
- Unknown but possible toxic effects on the embryo or fetus of a pregnant participant (Embryo-fetal toxicity)
The procedures done in this trial also have risks. The trial doctor or staff may have more information on these risks.
The tests, procedures, and actions from the participants are needed to make sure the trial results are accurate.
Confidential and proprietary
The Center for Information & Study on Clinical Research Participation (CISCRP) helped prepare this document. CISCRP is an independent non-profit organization focused on educating and informing the public about clinical research participation. CISCRP is not involved in recruiting participants for clinical trials, nor is it involved in conducting clinical research