PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE (PASSIVATE)

National University Heart Centre, Singapore

Status and phase: Terminated; Phase 2

Conditions: Acute Coronary Syndrome

Treatments: Drug: AZD5718; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04601467

2020/

Details and patient eligibility

About

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.

Full 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.

Enrollment: 243 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

243 participants in 2 patient groups, including a placebo group

AZD5718

Experimental group

Description:

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

Treatment:

Drug: AZD5718

Placebo

Placebo Comparator group

Description:

Patients will receive once daily oral dose of placebo matched to AZD5718 for 12 months

Treatment:

Drug: Placebo