Cangrelor on Top of anticoagUlation in Patients With myocaRdial Infarction-related Cardiogenic Shock/Cardiac Arrest receiVIng VA-ECMO

NCT ID: NCT06792643

Last Updated: 2025-01-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2025-12-31

Brief Summary

The SURVIVE trial aims to test whether using an anti-thrombotic regimen involving cangrelor can reduce bleeding risk while maintaining effective antithrombotic effects in patients on VA-ECMO due to cardiogenic shock (CS)/ cardiac arrest (CA) who undergo percutaneous coronary intervention (PCI). The investigators plan to achieve this by starting cangrelor on top of systemic anticoagulation with bivalirudin at a low dose, regularly monitoring platelet function, and adjusting the dose based on the results of platelet function assay (Multiplate®) to guarantee effective platelet P2Y12 pathway inhibition to achieve optimal platelet inhibition. Platelet function assays will be performed at various time points throughout the treatment timeframe. Cangrelor will then be stopped at the end of VA-ECMO support, and patients will be transitioned to oral P2Y12- inhibitors as per clinical guidelines.

Detailed Description

Veno-Arterial Extra Corporeal Membrane Oxygenation (VA-ECMO) is increasingly used to support patients throughout a spectrum of hemodynamic instability states ranging from severe cardiogenic shock (CS) to refractory cardiac arrest (CA). VA-ECMO, is thus often employed in clinical practice for the management of CS/CA complicating acute coronary syndromes (ACS). The interface of blood and VA-ECMO mechanical components, along with rotational forces generated by pump impellers configures a unique combination of prothrombotic and pro-haemorrhagic milieu (haemocompatibility). In this setting of competing thrombotic and hemorrhagic risks, optimal anti-thrombotic therapy remains ill-defined for patients undergoing percutaneous coronary intervention (PCI) for ACS on VA-ECMO. Theoretically, dual anti-platelet therapy (DAPT) consisting of aspirin plus an oral P2Y12 inhibitor should be associated with systemic anticoagulation (triple antithrombotic therapy). Platelet activation during ECMO support confers increased thrombotic risk, which, in the setting of ACS-related CS/CA, is worsened by the pro-thrombotic and pro-inflammatory state, the low-cardiac output with subsequent blood stasis and tissue hypoperfusion and possibly the need for myocardial revascularization procedure with stent implantation. At the same time, blood interaction with device foreign surfaces has been associated to reduced platelet surface expression of GpIb-GpIV, lower activated surface GpIIb-IIIa levels and blunted ADP-mediated aggregation, which translate into increased bleeding risk. Bleeding complications, however, exceed ischemic risk and triple antithrombotic therapy may confer an excess risk in this population prone to bleeding and may jeopardize patients' outcome. In this context of delicate haemostatic equilibrium several pharmacokinetic and pharmacodynamic factors limit the use of standard DAPT in addition to systemic anticoagulation, including the irreversible inhibiting effect of aspirin on platelets and the relatively long duration of action of oral P2Y12 inhibitors.

In addition, while GpIIb-IIIa inhibitors may offer a parenteral alternative antiplatelet agent, their use has been associated with increased transfusion need during VA-ECMO. The study hypothesis is that an anti-thrombotic regimen comprising cangrelor, an intravenous non-thienopyridine, reversible adenosine-diphosphate P2Y12 receptor antagonist, may reduce bleeding risk while providing adequate antithrombotic effect in patients on VA ECMO due to CS/CA who underwent PCI. Both the rapid onset and offset of action of this agent make it a particularly attractive option in patients at a high risk of both thrombotic and haemorrhagic complications, since a combination of a low starting dose of cangrelor coupled with regular platelet function tests potentially guarantees achieving adequate anti-platelet effect at the lowest possible cangrelor dose, in order to prevent ischemic events while minimizing bleeding risk.

Systemic anticoagulation will be performed with bivalirudin, titrated to achieve effective systemic anticoagulation and an activated thromboplastin time (aPTT) of 55-70'', as for routine clinical practice. Cangrelor will be started without bolus at a low dose of 0.125 mcg/kg/min and titrated (by 0.125 mcg/kg/min steps) based on the results of platelet function assay to guarantee effective platelet P2Y12 pathway inhibition. Platelet function will be assessed with the Multiplate analyser with the aim to reach and ADP-test <46 U. Platelet assay will be performed at baseline, 30 min after cangrelor infusion start, 12 hours after cangrelor infusion start, after any cangrelor dose modulation, regularly every 24 hours, at time of any thrombotic/bleeding event, and up to 48 hours from oral P2Y12-inhibitor initiation. Treatment with cangrelor will be discontinued at the end of VA-ECMO support, and patients will be loaded with oral P2Y12-inhibitors, as recommended for clinical practice.

Conditions

Cardiogenic Shock; Extracorporeal Membrane Oxygenation Complication; Platelet Dysfunction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cangrelor

Cangrelor will be started without bolus at a low dose of 0.125 mcg/kg/min and titrated (by 0.125 mcg/kg/min steps) based on the results of platelet function assay to guarantee effective platelet P2Y12 pathway inhibition.

Group Type: EXPERIMENTAL

Cangrelor

Intervention Type: DRUG

Cangrelor will be started without bolus at a low dose of 0.125 mcg/kg/min and titrated (by 0.125 mcg/kg/min steps) based on the results of platelet function assay to guarantee effective platelet P2Y12 pathway inhibition.

Interventions

Cangrelor

Cangrelor will be started without bolus at a low dose of 0.125 mcg/kg/min and titrated (by 0.125 mcg/kg/min steps) based on the results of platelet function assay to guarantee effective platelet P2Y12 pathway inhibition.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patients aged ≥18 years;
• ACS-related CS/CA patients undergoing PCI (either with or without stent implantation) and needing VA-ECMO support;
• Patients who received pre-hospital aspirin intravenous loading dose or patients naïve to any anti-thrombotic agent;
• Written informed consent

Exclusion Criteria

• Overt uncontrollable bleeding;
• Suspected intra-cranial haemorrhage;
• Patients who received any dose of any oral P2Y12-inhibitors;
• Patients with known history of stroke or Transient Ischaemic Attack (TIA);
• Patients with known hypersensitivity to the active substance (cangrelor) or to any of its excipients;
• Pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Anna Mara Scandroglio

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

IRCCS San Raffaele Hospital

Milan, Italy, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Marina Pieri, MD

Role: CONTACT

pieri.marina@hsr.it

0039 0226437722

Luca Baldetti, MD

Role: CONTACT

baldetti.luca@hsr.it

0039 0226437722

Other Identifiers

SURVIVE

Identifier Type: -

Identifier Source: org_study_id