Acute Coronary SyndromePhase 2PASSIVATENCT04601467
PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
A Phase 2 study testing AZD5718 in people with Acute Coronary Syndrome, run by National University Heart Centre, Singapore at 8 sites in 2 countries.
Trial summary
This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression… Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Acute Coronary Syndrome
- What is being tested?
- AZD5718
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 243 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 12 Jul 2021to 14 Aug 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- hospitalised for STEMI or non-STEMI, as defined by the 4th universal definition of MI
- underwent coronary angiography during the index hospitalisation showing at least one epicardial coronary artery with ≥50% stenosis and a 2nd epicardial coronary artery with ≥20% stenosis on the coronary angiogram
- Body Mass Index (BMI) ≥18 to ≤40 kg/m2
- White Blood Cell count ≥ 7.0 X 103/uL during admission
Who cannot join
- Prior coronary artery bypass grafting (CABG)
- CABG planned within 12 months of admission
- Known history of drug or alcohol abuse within 5 years of screening
- History of QT prolongation associated with other medications that required discontinuation of that medication
- Congenital long QT syndrome
- Systolic blood pressure persistently <90 mm Hg or HR<40 beats per minute at time of enrolment
Show all 16Show fewer
- ALT >2 x ULN, cirrhosis, recent hepatitis, or positive screening test for hepatitis B (hepatitis B surface antigen) or other viral hepatitis
- Uncontrolled Type 1 or Type 2 DM defined as HbA1c >10% or 74.9 mmol/mol (by IFCC)
- Any planned coronary revascularisation, valve surgery, or cardiac resynchronisation within 7 months after randomisation
- Any concomitant medications known to be associated with Torsades de Pointes or potent inducers of cytochrome P450 3A4 (CYP3A4)
- Planned treatment with zileuton, leukotriene receptor antagonists (e.g., montelukast) during trial
- Participated in another interventional clinical study with an investigational pharmaceutical product during the last 3 months
- Known hypersensitivity to drugs with a similar chemical structure or class of study drugs or any of the excipients of the product
- Known conditions that either increase the risk of performing the CT or make the procedure technically impractical
- No severe asthma attack that require emergency treatment or hospitalisation in the past 6 months
- Had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks of Screening Visit
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Singapore6 sites
Changi General Hospital (CGH)
Singapore
Khoo Teck Puat Hospital (KTPH)
Singapore
National Heart Centre Singapore (NHCS)
Singapore
National University Heart Centre, Singapore (NUHCS)
Singapore
Ng Teng Fong General Hospital (NTFGH)
Singapore
Tan Tock Seng Hospital (TTSH)
Singapore
New Zealand2 sites
North Shore Hospital
Auckland
Christchurch Heart Institute (CHI)
Christchurch
About this study
This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression as measured on serial computer tomographic coronary angiography.
Read the detailed description
PASSIVATE is a randomized, double-blind, placebo-controlled Phase IIa trial that investigates how 12 months of treatment with AZD5718 modifies coronary plaque volume. Patients with recent STEMI or NSTEMI will receive an additional oral dose of AZD5718 (or placebo) once daily to standard clinical care for 12 months. The primary hypothesis being tested in PASSIVATE is that 12 months of treatment with AZD5718 attenuates the progression of non-calcified plaque (NCP) volume on serial computed tomography coronary angiography (CTCA) studies.
Patients who gave consent (within 60 days after their index event) will undergo a CTCA scan and start treatment (AZD5718 or Placebo). The treatment duration will be 12 months. During the treatment period, patients will come to the clinic for follow-ups. At 12 months (end treatment), the patients will undergo their 2nd CTCA scan. A follow-up visit will be performed 4 weeks after the last dose in order to ensure the safety and well-being of the patients.
- Conditions
- Acute Coronary Syndrome
- Being tested
- AZD5718, Placebo
- Keywords
- Acute Myocardial Infarction, Computed Tomography Coronary Angiography
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5718Drug
Oral dose of AZD5718 (tablet) once daily for 12 months
PlaceboDrug
Oral dose of matching placebo (tablet) once daily for 12 months
| Study group | Role | What they receive |
|---|---|---|
| AZD5718 | Experimental | Patients will receive once daily oral dose of AZD5718 for 12 months Receives: Drug: AZD5718 |
| Placebo | Placebo comparator | Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in noncalcified coronary artery plaque volume (NCPV)
Percent change in NCPV (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment
Measured: Baseline (before treatment) and after 12 months of treatment
Secondary outcomes (4)
Change in CT peri vascular (coronary) adipose tissue (PVAT)
To assess whether AZD5718 reduces coronary inflammation
Measured: Baseline (before treatment) and after 12 months of treatment
Change in total plaque volume (mm3)
Percent change in total plaque volume (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment
Measured: Baseline (before treatment) and after 12 months of treatment
Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)
Percent change in LVEF (%), as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment
Measured: Baseline (before treatment) and after 12 months of treatment
Change in levels of urinary LTE4 (u-LTE4)
To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of u-LTE4 in AMI patients
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2020
- Study start12 Jul 2021
- Primary completion27 May 2024
- Study completion14 Aug 2024
Why it stopped: The study was terminated early on 14th September 2023 by the main funding company because of financial futility. We were able to enroll 243 of the initial planned 360 participants and randomised 209 participants of the intial planned 286.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Heart Centre, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, University of Otago
- Responsible party
- Principal investigator, Mark Chan, National University Heart Centre, Singapore
- Investigators
- Mark Chan, Principal investigator, National University Heart Centre, SingaporeDerek Hausenloy, Principal investigator, National Heart Centre SingaporeA. Mark Richards, Study chair, National University Heart Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04601467
- Sponsor's protocol ID
- 2020/
- Acronym
- PASSIVATE
- Status last verified
- Apr 2025
- First submitted
- 11 Sep 2020
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share anonmyised IPD upon reasonable request from academic investigators employed by universities and/or healthcare organisations to the study PIs.
Publications
Ericsson H, Nelander K, Lagerstrom-Fermer M, Balendran C, Bhat M, Chialda L, Gan LM, Heijer M, Kjaer M, Lambert J, Lindstedt EL, Forsberg GB, Whatling C, Skrtic S. Initial Clinical Experience with AZD5718, a Novel Once Daily Oral 5-Lipoxygenase Activating Protein Inhibitor. Clin Transl Sci. 2018 May;11(3):330-338. doi: 10.1111/cts.12546. Epub 2018 Mar 8.
PubMed 29517132Pettersen D, Broddefalk J, Emtenas H, Hayes MA, Lemurell M, Swanson M, Ulander J, Whatling C, Amilon C, Ericsson H, Westin Eriksson A, Granberg K, Plowright AT, Shamovsky I, Dellsen A, Sundqvist M, Nagard M, Lindstedt EL. Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease. J Med Chem. 2019 May 9;62(9):4312-4324. doi: 10.1021/acs.jmedchem.8b02004. Epub 2019 Mar 26.
PubMed 30869888
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
- ClinicalTrials.gov ID
- NCT04601467
- Acronym / sponsor ID
- PASSIVATE / 2020/
- Conditions
- Acute Coronary Syndrome
- Keywords
- Acute Myocardial Infarction, Computed Tomography Coronary Angiography
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early on 14th September 2023 by the main funding company because of financial futility. We were able to enroll 243 of the initial planned 360 participants and randomised 209 participants of the intial planned 286.
- Enrolment
- 243 participants (actual)
- Lead sponsor
- National University Heart Centre, SingaporeUniversity, hospital or other
- Collaborators
- AstraZeneca, University of Otago
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 27 May 2024 (actual)
- Study completion
- 14 Aug 2024 (actual)
- First posted
- 23 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression as measured on serial computer tomographic coronary angiography.
Detailed description
PASSIVATE is a randomized, double-blind, placebo-controlled Phase IIa trial that investigates how 12 months of treatment with AZD5718 modifies coronary plaque volume. Patients with recent STEMI or NSTEMI will receive an additional oral dose of AZD5718 (or placebo) once daily to standard clinical care for 12 months. The primary hypothesis being tested in PASSIVATE is that 12 months of treatment with AZD5718 attenuates the progression of non-calcified plaque (NCP) volume on serial computed tomography coronary angiography (CTCA) studies.
Patients who gave consent (within 60 days after their index event) will undergo a CTCA scan and start treatment (AZD5718 or Placebo). The treatment duration will be 12 months. During the treatment period, patients will come to the clinic for follow-ups. At 12 months (end treatment), the patients will undergo their 2nd CTCA scan. A follow-up visit will be performed 4 weeks after the last dose in order to ensure the safety and well-being of the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD5718 | Experimental | Drug: AZD5718Patients will receive once daily oral dose of AZD5718 for 12 months |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive once daily oral dose of placebo matched to AZD5718 for 12 months |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- hospitalised for STEMI or non-STEMI, as defined by the 4th universal definition of MI
- underwent coronary angiography during the index hospitalisation showing at least one epicardial coronary artery with ≥50% stenosis and a 2nd epicardial coronary artery with ≥20% stenosis on the coronary angiogram
- Body Mass Index (BMI) ≥18 to ≤40 kg/m2
- White Blood Cell count ≥ 7.0 X 103/uL during admission
Key exclusion criteria (16 listed)
- Prior coronary artery bypass grafting (CABG)
- CABG planned within 12 months of admission
- Known history of drug or alcohol abuse within 5 years of screening
- History of QT prolongation associated with other medications that required discontinuation of that medication
- Congenital long QT syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD5718Oral dose of AZD5718 (tablet) once daily for 12 months | Drug | AZD5718 |
| PlaceboOral dose of matching placebo (tablet) once daily for 12 months | Drug | Placebo |
Primary outcome
Change in noncalcified coronary artery plaque volume (NCPV)
Time frame: Baseline (before treatment) and after 12 months of treatment
Percent change in NCPV (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment
4 secondary outcomes
Change in CT peri vascular (coronary) adipose tissue (PVAT)
Time frame: Baseline (before treatment) and after 12 months of treatment
Change in total plaque volume (mm3)
Time frame: Baseline (before treatment) and after 12 months of treatment
Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)
Time frame: Baseline (before treatment) and after 12 months of treatment
Change in levels of urinary LTE4 (u-LTE4)
Time frame: 12 months
Results and safety
The study was stopped early (reason given: The study was terminated early on 14th September 2023 by the main funding company because of financial futility. We were able to enroll 243 of the initial planned 360 participants and randomised 209 participants of the intial planned 286.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
- Background: PubMed 29517132Ericsson H, Nelander K, Lagerstrom-Fermer M, Balendran C, Bhat M, Chialda L, Gan LM, Heijer M, Kjaer M, Lambert J, Lindstedt EL, Forsberg GB, Whatling C, Skrtic S. Initial Clinical Experience with AZD5718, a Novel Once Daily Oral 5-Lipoxygenase Activating Protein Inhibitor. Clin Transl Sci. 2018 May;11(3):330-338. doi: 10.1111/cts.12546. Epub 2018 Mar 8.
- Background: PubMed 30869888Pettersen D, Broddefalk J, Emtenas H, Hayes MA, Lemurell M, Swanson M, Ulander J, Whatling C, Amilon C, Ericsson H, Westin Eriksson A, Granberg K, Plowright AT, Shamovsky I, Dellsen A, Sundqvist M, Nagard M, Lindstedt EL. Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease. J Med Chem. 2019 May 9;62(9):4312-4324. doi: 10.1021/acs.jmedchem.8b02004. Epub 2019 Mar 26.
- Individual participant dataSharing planned: Yes. We will share anonmyised IPD upon reasonable request from academic investigators employed by universities and/or healthcare organisations to the study PIs.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Chan principal investigator
National University Heart Centre, Singapore
Derek Hausenloy principal investigator
National Heart Centre Singapore
A. Mark Richards study chair
National University Heart Centre, Singapore
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD5718 in people with Acute Coronary Syndrome, run by National University Heart Centre, Singapore at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Singapore, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated early on 14th September 2023 by the main funding company because of financial futility. We were able to enroll 243 of the initial planned 360 participants and randomised 209 participants of the intial planned 286.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in noncalcified coronary artery plaque volume (NCPV) (time frame: Baseline (before treatment) and after 12 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04601467, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025.