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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04601467




Registration number
NCT04601467
Ethics application status
Date submitted
11/09/2020
Date registered
23/10/2020
Date last updated
15/12/2022

Titles & IDs
Public title
PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
Scientific title
PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE
Secondary ID [1] 0 0
2020/
Universal Trial Number (UTN)
Trial acronym
PASSIVATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Coronary Syndrome 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD5718
Treatment: Drugs - Placebo

Experimental: AZD5718 - Patients will receive once daily oral dose of AZD5718 for 12 months

Placebo comparator: Placebo - Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months


Treatment: Drugs: AZD5718
Oral dose of AZD5718 (tablet) once daily for 12 months

Treatment: Drugs: Placebo
Oral dose of matching placebo (tablet) once daily for 12 months
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in noncalcified coronary artery plaque volume (NCPV)
Timepoint [1] 0 0
Baseline (before treatment) and after 12 months of treatment
Secondary outcome [1] 0 0
Change in CT pericoronary adipose tissue (PCAT)
Timepoint [1] 0 0
Baseline (before treatment) and after 12 months of treatment
Secondary outcome [2] 0 0
Change in total plaque volume (mm3)
Timepoint [2] 0 0
Baseline (before treatment) and after 12 months of treatment
Secondary outcome [3] 0 0
Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)
Timepoint [3] 0 0
Baseline (before treatment) and after 12 months of treatment
Secondary outcome [4] 0 0
Plasma concentrations of AZD5718
Timepoint [4] 0 0
12 month
Secondary outcome [5] 0 0
Change in levels of urinary LTE4 (u-LTE4)
Timepoint [5] 0 0
12 months

Eligibility
Key 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
Minimum age
21 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
360
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Cairns Hospital - Cairns
Recruitment hospital [2] 0 0
Monash Medical Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Cairns
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
Singapore
State/province [3] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Other
Name
National University Heart Centre, Singapore
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04601467
Trial related presentations / 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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Mark Chan
Address 0 0
National University Heart Centre, Singapore
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sock Hwee Tan
Address 0 0
Country 0 0
Phone 0 0
+65 67795555
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04601467