Clinical trial NCT03043274
Conditions: STEMI - ST Elevation Myocardial Infarction
Sponsor: Khaled Ziada, MD
Start date: 2017-01-01; Completion date: 2019-05-01
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates differences in the extent of myocardial necrosis noted by cardiac MRI in patients with ST-elevation myocardial infarction randomized to receive cangrelor during their percutaneous coronary intervention and compares them to patients randomized to not receive cangrelor.

Detailed description:
Cangrelor is a direct-acting and reversible intravenously administered platelet inhibitor approved as an adjunct to percutaneous intervention (PCI) for reducing the risk of periprocedural myocardial infarction, repeat coronary revascularization, and stent thrombosis. As it has a quick onset of action (2 minutes) compared to traditional oral platelet inhibitors, cangrelor is emerging as an important new option for use in patients undergoing percutaneous intervention who have not been treated with oral platelet inhibitors.

Furthermore, multiple studies have demonstrated that patients with ST-elevation myocardial infarction (STEMI) who undergo emergent PCI do not have optimal platelet inhibition even after administration of a loading dose of traditional oral platelet inhibitors. However, the clinical significance of complete platelet inhibition around the time of PCI is not fully understood.

The primary objective is to characterize the utility of immediate platelet inhibition with intravenous cangrelor in patients presenting with an acute STEMI by assessing the extent of infarct size (either enzymatically or by imaging). If the findings are favorable, this may suggest that immediate platelet inhibition is an important part of care in this patient population.

Arms: arm 1: Approximately 30 patients in this arm will receive standard STEMI care but will also receive standard dosing of cangrelor at the time of their PCI. arm 2: Approximately 30 patients in this arm will receive standard STEMI but will not receive cangrelor at the time of their PCI.
Interventions: intervention 1: Cangrelor
Intervention descriptions: intervention 1: Cangrelor 30 mcg/kg bolus followed by a 4 mcg/kg/min intravenous infusion prior to PCI will be given. It will be continued for ≥ 2 hours or for the duration of the procedure, whichever is longer.

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 Study Title: Cangrelor in ST-Elevation Myocardial Infarction to Decrease Infarct Size 
Institution/Site:  
University of Kentucky-Gill Heart Institute 
Document (Approval/Update) Date: 
12/13/2017 
NCT Number: 
NCT03043274 
IRB Number 
16-0990-F6A 
Coversheet created: 
05/22/2020 
 
 
 
 


Methods:  
Patients presenting with STEMI from February 2017 to February 2019 at the University of 
Kentucky hospitals were randomized to receive either cangrelor and ticagrelor or ticagrelor alone 
(standard group) before PPCI. All patients provided written informed consent approved by the 
institutional review board. Patients who were hemodynamically unstable with evidence of cardiogenic 
shock, mechanically intubated, already on dual antiplatelet therapy, or received thrombolytics were 
excluded. Patients received cangrelor with a dose of 30 mcg/kg bolus followed by a 4 mcg/kg/min 
intravenous infusion, started prior to PPCI and continued for 2 hours or for the duration of the procedure, 
whichever is longer. The detailed study protocol was previously reported (NCT03043274). The study was 
terminated because of slow recruitment. Peripheral blood (PB) samples were collected at the beginning of 
the PPCI procedure and before intervention (baseline), at 10-minute after starting study drug and at the 
end of the procedure to assess platelet aggregation in response to adenosine diphosphate (ADP) and 
thrombin receptor activating peptide (TRAP) using Multiplate system. Additionally, we examined 
circulating pro-inflammatory cells, cytokine levels, and surrogate markers for neutrophil extracellular 
traps (NETs), such as plasma elastase and myeloperoxidase (MPO) in the PB before PPCI, then at 6 and 
12 hours after randomization using Milliplex human cytokine magnetic kit (MILLIPLEX MAP for 
Luminex xMap Technology, Millipore, USA) or standard ELISA kits (BD biosciences, USA) according 
to the manufacturer’s protocol. Myocardial damage/edema (defined as myocardial tissue enhancement 
greater than 5 SD) were assessed using late gadolinium enhancement (LGE) on cardiac magnetic 
resonance at 48 hours (before hospital discharge) and at 3 months after randomization (6). Troponin I was 
measured during the first 12 hours after iniating the study drug. 
For baseline characteristics, categorical variables were presented as frequencies and proportions 
and were compared using chi-square test. Continuous variables were summarized as mean with standard 
deviations or median with interquartile ranges as appropriate, and were compared using student T-test or 
Mann Whitney U test. ADP-and-TRAP-induced platelet aggregations, inflammatory cells, pro-


inflammatory cytokines, total elastase and elastase-myeloperoxidase, left ventricular ejection fraction 
(LVEF), and LGE-5SD were compared between both groups. All statistical analyses were performed 
using SPSS software (IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp 
Released 2016) and GraphPad Prism 8 (San Diego, USA).