Comparative Efficacy of Apixaban Versus Warfarin in Thrombus Resolution for Patients with Left Ventricular Thrombosis Post-Acute Myocardial Infarction

The primary objective of this study is to compare the effect of **apixaban** versus **warfarin** on thrombus resolution in patients with left ventricular thrombus following an acute myocardial infarction. This is clinically relevant as effective thrombus resolution is crucial in preventing further cardiovascular complications and improving patient outcomes after an acute myocardial infarction.

Secondary objectives include:

• Comparing apixaban versus warfarin with respect to clinically relevant bleeding.
• Comparing apixaban versus warfarin with respect to major bleeding.
• Comparing apixaban versus warfarin with respect to separate bleeding outcomes.
• Comparing apixaban versus warfarin with respect to major adverse cardiovascular events.
• Comparing apixaban versus warfarin with respect to net clinical benefit defined as major adverse cardiovascular events and clinically relevant bleeding.
• Comparing apixaban versus warfarin with respect to ischemic stroke and systemic embolism.
• Evaluating the rate of thrombus recurrence one year after the index event.

The clinical trial involves participants diagnosed with **left ventricular thrombosis** following an **acute myocardial infarction (AMI)**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a confirmed diagnosis of left ventricular thrombus via transthoracic echocardiogram (TTE) or, if inconclusive, through cardiac magnetic resonance imaging (MRI) or computed tomography (CT) within 1 to 28 days post-AMI. The trial does not specifically target a vulnerable population. Lifestyle factors such as diet, physical activity, or habits are not specified as part of the study criteria. The sponsor has not provided information regarding the total number of participants. Key inclusion criteria include the requirement for female participants of childbearing potential to provide a negative pregnancy test and adhere to effective contraception methods during and after the study. The trial aims to compare the effects of apixaban versus warfarin on thrombus resolution in this patient group.

The clinical trial is designed as a **randomized**, open-label, parallel-arm study comparing the efficacy of **apixaban** versus **warfarin** in patients with left ventricular thrombus following an acute myocardial infarction. The trial aims to evaluate thrombus resolution as the primary endpoint, assessed via transthoracic echocardiogram (TTE) at three months, with cardiac magnetic resonance imaging (MRI) or computed tomography (CT) as alternatives if TTE results are inconclusive. Secondary endpoints include clinically relevant bleeding, major adverse cardiovascular events, and recurrence of left ventricular thrombus at 12 months. The trial is categorized as a Phase IV, low-intervention study, with an estimated completion date of December 31, 2028.

Participants will be involved in the study for a maximum treatment period of three months. The study begins with a screening visit to confirm eligibility, including a diagnosis of left ventricular thrombus via TTE, MRI, or CT within 28 days post-acute myocardial infarction. Participants must be at least 18 years old and provide written informed consent. Women of childbearing potential are required to have a negative pregnancy test and agree to use effective contraception during the study and for three months after the last dose of the study drug.

Following the inclusion visit, participants will be randomized to receive either apixaban or warfarin. Study visits will occur at regular intervals to monitor thrombus resolution and assess for any adverse events, including bleeding complications. The end-of-study visit will occur at the three-month mark, where the primary endpoint will be evaluated. Participants may be withdrawn from the study early if they experience significant adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial's design ensures rigorous monitoring and assessment to achieve its primary objective of comparing the efficacy of the two anticoagulants in thrombus resolution.

The clinical trial involves the administration of **Eliquis** in two different dosages as part of the experimental treatment. **Eliquis 2.5 mg film-coated tablets** and **Eliquis 5 mg film-coated tablets** are both utilized. The active substance in these formulations is **apixaban**, a chemical compound. The pharmaceutical form is a film-coated tablet, and the route of administration is oral. The maximum daily dose for both dosages is 10 mg, with a total maximum dose of 10 mg over a treatment period of up to 3 months. The tablets are manufactured by Bristol-Myers Squibb/Pfizer EEIG and are not formulated for pediatric use.

As a comparator treatment, **Waran 2.5 mg tabletter** is used. The active substance in this formulation is **warfarin sodium**, also a chemical compound. The pharmaceutical form is a tablet, and the route of administration is oral. The maximum daily dose is 2.5 mg, with a total maximum dose of 2.5 mg over a treatment period of up to 3 months. This product is manufactured by Orifarm Healthcare A/S and serves as an oral anticoagulant in the study.

Additionally, the trial employs auxiliary treatments for imaging purposes. **OPTISON 0.19 mg/ml dispersion for injection** is used, containing the active substance **perflutren**, a chemical compound. The pharmaceutical form is a dispersion for injection, with a maximum daily dose of 3.0 ml and a total maximum dose of 8.7 ml over a treatment period of 1 day. The route of administration is injection, and the product is manufactured by GE Healthcare AS.

Another auxiliary treatment is **SonoVue 8 microlitres/mL powder and solvent for dispersion for injection**, which contains **sulfur hexafluoride** as the active substance. This chemical compound is provided in a dispersion for injection form. The maximum daily dose is 8.0 microlitres, with a total maximum dose of 2.0 ml over a treatment period of 1 day. The route of administration is injection, and the product is manufactured by Bracco International BV.

The efficacy of the clinical trial will be assessed by comparing the effect of **apixaban** versus warfarin on thrombus resolution in patients with left ventricular thrombus following an acute myocardial infarction. The primary endpoint for evaluating efficacy is thrombus resolution, which will be assessed using transthoracic echocardiogram (TTE), preferably contrast-enhanced, at 3 months. If TTE results are inconclusive, cardiac magnetic resonance imaging (MRI) or cardiac computed tomography (CCT) is recommended to evaluate the primary endpoint.

Secondary endpoints include clinically relevant bleeding as defined by the Bleeding Academy Research Consortium (BARC) 2, 3, or 5 bleeding, major bleeding (BARC 3 or 5), and individual bleeding endpoints such as fatal bleeding, intracranial hemorrhage, gastrointestinal bleeding, urogenital bleeding, and bleeding from other sources. Additionally, major adverse cardiovascular events (MACE), which is a composite of non-fatal myocardial infarction, non-fatal ischemic stroke, and cardiovascular death, will be assessed. The net clinical benefit, defined as a composite of MACE and BARC 2, 3, or 5 bleeding, ischemic stroke and systemic embolism, and recurrence of left ventricular thrombus at 12 months, will also be evaluated.