Evaluation of Cangrelor and Bivalirudin in Myocardial Infarction-Related Cardiogenic Shock/Cardiac Arrest with VA-ECMO/Impella Support

The primary objective of this study is to evaluate the **feasibility**, **efficacy**, and **safety** of an antithrombotic therapy regimen combining bivalirudin and cangrelor in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock (CS) or cardiac arrest (CA). The study aims to prevent thrombotic events while minimizing hemorrhagic events by titrating the therapy based on platelet function assay results. This is clinically relevant as it addresses the high incidence of bleeding associated with conventional antithrombotic therapies, potentially offering a safer and more effective treatment option for this high-risk patient population.

The clinical trial involves **adult patients** undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock (CS) or cardiac arrest (CA). The study population includes both male and female participants aged 18 years and older. The trial does not involve a vulnerable population. Participants are selected based on their need for temporary mechanical circulatory support (tMCS) with VA-ECMO or Impella, and they may have received a pre-hospital intravenous loading dose of aspirin or be naïve to any anti-thrombotic agent. The sponsor has not provided the total number of participants. The trial aims to evaluate the feasibility, efficacy, and safety of an antithrombotic therapy combining bivalirudin and cangrelor, titrated based on platelet function assay results, to prevent thrombotic events and minimize hemorrhagic events in this specific patient group.

The clinical trial is designed to evaluate the **efficacy** and safety of an antithrombotic therapy combining bivalirudin and **cangrelor tetrasodium** in adult patients experiencing cardiogenic shock or cardiac arrest related to acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI) with VA-ECMO or Impella support. This is a phase 2, single-arm, single-center trial. The study will assess the feasibility of this therapeutic approach, focusing on the prevention of thrombotic events and the minimization of hemorrhagic events. The trial is expected to commence on November 15, 2023, and conclude by November 15, 2026.

Participants will be involved in the study for a maximum treatment period of three days, during which they will receive cangrelor intravenously, starting at a dose of 0.125 mcg/kg/min, with adjustments made based on platelet function assay results. The primary endpoints include the occurrence of thrombotic and bleeding adverse events during cangrelor infusion, with major bleeding defined according to the Bleeding Academic Research Consortium (BARC) criteria. The inclusion criteria specify that participants must be male or female, aged 18 years or older, undergoing PCI for ACS-related cardiogenic shock or cardiac arrest, and requiring mechanical circulatory support with VA-ECMO or Impella. Written informed consent is required, either directly from the patient or from a legal representative if the patient is unconscious.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will be conducted to monitor the safety and efficacy of the treatment, with assessments of thrombotic and bleeding events. The end-of-study visit will occur at the conclusion of the treatment period, where final evaluations will be made. Participants may be terminated early from the study if they experience significant adverse events or if they withdraw consent. The trial is not classified as low intervention, and it is conducted under the regulatory framework of a phase 2 clinical trial.

The clinical trial involves the administration of **Kengrexal**, a pharmaceutical product containing the active substance **cangrelor tetrasodium**. Kengrexal is provided in the form of a powder for concentrate, intended for solution for injection or infusion. The pharmaceutical form is specifically a solution for injection/infusion, and the route of administration is **intravenous use**. The dosage regimen involves a maximum daily dose of 0.75 mg/kg, with a total maximum dose not exceeding 100 mg. The treatment period is limited to a maximum of 3 days. The product is manufactured by Chiesi Farmaceutici S.p.A. and is not a pediatric formulation.

In addition to the experimental treatment with Kengrexal, the study protocol includes the use of **bivalirudin** as part of the antithrombotic therapy. Bivalirudin is administered in conjunction with cangrelor, with dosing titrated based on the results of platelet function assays. This combination aims to prevent thrombotic events while minimizing hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock (CS) or cardiac arrest (CA).

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study is designed to assess the feasibility, efficacy, and safety of the combined antithrombotic therapy, with a focus on the prevention of thrombotic events and the minimization of hemorrhagic events.

The efficacy of the clinical trial will be assessed by evaluating the prevention of thrombotic events in patients with **myocardial infarction** related cardiogenic shock or cardiac arrest receiving VA-ECMO and/or Impella support. The primary efficacy endpoint is the occurrence of thrombotic adverse events during the time of cangrelor infusion. This will be measured alongside safety endpoints, which include the occurrence of bleeding adverse events, specifically major bleeding events defined as type 3b or 5 according to the Bleeding Academic Research Consortium (BARC) criteria.