Back to resultsPASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE (PASSIVATE)
Primary Purpose
Acute Coronary Syndrome
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD5718
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Coronary Syndrome focused on measuring Acute Myocardial Infarction, Computed Tomography Coronary Angiography
Eligibility Criteria
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
Sites / Locations
- Cairns Hospital
- Monash Medical CentreRecruiting
- North Shore HospitalRecruiting
- Christchurch Heart Institute (CHI)Recruiting
- Changi General Hospital (CGH)Recruiting
- Khoo Teck Puat Hospital (KTPH)Recruiting
- National Heart Centre Singapore (NHCS)Recruiting
- National University Heart Centre, Singapore (NUHCS)Recruiting
- Ng Teng Fong General Hospital (NTFGH)Recruiting
- Tan Tock Seng Hospital (TTSH)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD5718
Placebo
Arm Description
Patients will receive once daily oral dose of AZD5718 for 12 months
Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Change in CT pericoronary adipose tissue (PCAT)
To assess whether AZD5718 reduces coronary inflammation
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
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
Plasma concentrations of AZD5718
To assess the PK of AZD5718 after repeated oral dosing for 12 months
Change in levels of urinary LTE4 (u-LTE4)
To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of u-LTE4 in AMI patients
Full Information
NCT ID
NCT04601467
First Posted
September 11, 2020
Last Updated
December 13, 2022
Sponsor
National University Heart Centre, Singapore
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT04601467
Brief Title
PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
Acronym
PASSIVATE
Official Title
PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 12, 2021 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National University Heart Centre, Singapore
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multi-center study conducted at 13 sites in 3 countries (Singapore, New Zealand, and the Australia). Approximately 260 patients with an acute myocardial infarction (AMI) will be randomized in a ratio of 1:1 ratio to receive AZD5718 125 mg or placebo for 12 months.
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 30 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome
Keywords
Acute Myocardial Infarction, Computed Tomography Coronary Angiography
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
360 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AZD5718
Arm Type
Experimental
Arm Description
Patients will receive once daily oral dose of AZD5718 for 12 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months
Intervention Type
Drug
Intervention Name(s)
AZD5718
Intervention Description
Oral dose of AZD5718 (tablet) once daily for 12 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral dose of matching placebo (tablet) once daily for 12 months
Primary Outcome Measure Information:
Title
Change in noncalcified coronary artery plaque volume (NCPV)
Description
Percent change in NCPV (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Secondary Outcome Measure Information:
Title
Change in CT pericoronary adipose tissue (PCAT)
Description
To assess whether AZD5718 reduces coronary inflammation
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Change in total plaque volume (mm3)
Description
Percent change in total plaque volume (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)
Description
Percent change in LVEF (%), as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Plasma concentrations of AZD5718
Description
To assess the PK of AZD5718 after repeated oral dosing for 12 months
Time Frame
12 month
Title
Change in levels of urinary LTE4 (u-LTE4)
Description
To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of u-LTE4 in AMI patients
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Change in low attenuation plaque burden
Description
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
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Change in levels of ex vivo stimulated plasma leukotriene B4 (LTB4)
Description
To assess the effect of AZD5718 on LTB4 levels in ex vivo stimulated human plasma by liquid chromatography-tandem mass spectrometry
Time Frame
12 months
Title
Change in plasma hs-CRP concentration
Description
To assess the changes in circulating hs-CRP concentrations from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Change in plasma troponin concentration
Description
To assess the changes in circulating troponin concentrations from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Change in plasma NT-proBNP concentration
Description
To assess the changes in circulating NT-proBNP concentrations from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Echocardiographic assessment: Change in LV global longitudinal strain
Description
Percent change in LV global longitudinal strain, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Echocardiographic assessment: Change in global circumferential strain
Description
Percent change in global circumferential strain, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
Title
Echocardiographic assessment: Change in longitudinal early diastolic strain rate
Description
Percent change in longitudinal early diastolic strain rate, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment
Time Frame
Baseline (before treatment) and after 12 months of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sock Hwee Tan
Phone
+65 67795555
Email
mdctshw@nus.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Chan
Organizational Affiliation
National University Heart Centre, Singapore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Derek Hausenloy
Organizational Affiliation
National Heart Centre Singapore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
A. Mark Richards
Organizational Affiliation
National University Heart Centre, Singapore
Official's Role
Study Chair
Facility Information:
Facility Name
Cairns Hospital
City
Cairns
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Monash Medical Centre
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
North Shore Hospital
City
Auckland
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Christchurch Heart Institute (CHI)
City
Christchurch
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Changi General Hospital (CGH)
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Khoo Teck Puat Hospital (KTPH)
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Name
National Heart Centre Singapore (NHCS)
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Name
National University Heart Centre, Singapore (NUHCS)
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Ng Teng Fong General Hospital (NTFGH)
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Tan Tock Seng Hospital (TTSH)
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29517132
Citation
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.
Results Reference
background
PubMed Identifier
30869888
Citation
Pettersen 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.
Results Reference
background
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PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
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