Acute Coronary Syndrome
Conditions
Keywords
Acute Myocardial Infarction, Computed Tomography Coronary Angiography
Brief 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 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.
Interventions
DRUGAZD5718
Oral dose of AZD5718 (tablet) once daily for 12 months
DRUGPlacebo
Oral dose of matching placebo (tablet) once daily for 12 months
Sponsors
AstraZeneca
University of Otago
National University Heart Centre, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
CT coronary angiogram core laboratory
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in noncalcified coronary artery plaque volume (NCPV) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CT peri vascular (coronary) adipose tissue (PVAT) | Baseline (before treatment) and after 12 months of treatment | To assess whether AZD5718 reduces coronary inflammation |
| Change in total plaque volume (mm3) | Baseline (before treatment) and after 12 months of treatment | Percent change in total plaque volume (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment |
| Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF) | Baseline (before treatment) and after 12 months of treatment | Percent change in LVEF (%), as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment |
| Change in levels of urinary LTE4 (u-LTE4) | 12 months | To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of u-LTE4 in AMI patients |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in low attenuation plaque burden | Baseline (before treatment) and after 12 months of treatment | Percent change in low attenuation (\<30 HU) plaque volume (mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment |
| Change in plasma hs-CRP concentration | Baseline (before treatment) and after 12 months of treatment | To assess the changes in circulating hs-CRP concentrations from baseline (before treatment) to after 12-month of treatment |
| Echocardiographic assessment: Change in LV global longitudinal strain | Baseline (before treatment) and after 12 months of treatment | Percent change in LV global longitudinal strain, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment |
| Echocardiographic assessment: Change in global circumferential strain | Baseline (before treatment) and after 12 months of treatment | Percent change in global circumferential strain, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment |
| Echocardiographic assessment: Change in longitudinal early diastolic strain rate | Baseline (before treatment) and after 12 months of treatment | Percent change in longitudinal early diastolic strain rate, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment |
Countries
New Zealand, Singapore
Outcome results
None listed