Pan-Cardio-Genetics Clot Assessment in Acute Coronary Syndromes

STEMI - ST Elevation Myocardial Infarction Clinical Trial

— PGCA-ACS  

Official title:

Pan-Cardio-Genetics Clot Assessment in Acute Coronary Syndromes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03832153
• Other study ID #: 20181028
• Status: Withdrawn
• Start date: January 20, 2019
• Est. completion date: March 30, 2022

Study information

• Verified date: February 2022
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Acute myocardial infarction with ST elevation (STEMI) is one of the leading causes of mortality. Although the presence of thrombus in STEMI patients has been linked to adverse outcomes, routine thrombus aspiration has not been proven effective. A potential explanation could be that patients with STEMI should be risk-stratified. Thus, a more personalized approach in treating these patients is stressfully required. This proposal aims to establish the required interdisciplinary infrastructure for developing a risk-stratification model by implementing clinical, laboratory and angiographic data with molecular knowledge obtained by using innovative technologies, such as data from nano/micro-Computed tomography and circulating microRNAs. Two hundred consecutive patients with STEMI undergoing thrombus aspiration will be enrolled in the study and will be followed-up for one year for Major Adverse Cardiac and Cerebrovascular events (MACCE). The proposed approach will shed light on the pathophysiological mechanisms and broaden the investigator's understanding of the complex cellular and molecular interactions in the STEMI setting that, along with clinical parameters, affect patient outcomes. Furthermore, it will enable the identification of certain circulating micro-RNAs as cardiovascular disease biomarkers and it will help clinicians to better stratify the cardiovascular and cerebrovascular risk of patients with STEMI. As part of the work, important characteristics of aspirated thrombi will be assessed for the first time (such as volume, density and shape) and will be linked to patient outcomes. All this information will be incorporated into one in-vitro model, which will be developed using bioprinting and microfluidics methodologies. The in-vitro model will facilitate: (i) the in-depth exploration of the pathophysiological mechanisms in patients with STEMI; and (ii) the therapeutic optimization of innovative nanocarriers/nanomedicines with thrombolytic efficacy. Clearly, the study improves personalized cardiovascular medicine approaches, by considering individual patient clinical assessment in a way that empowers the precision in diagnosis and therapy.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 30, 2022
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with symptoms of myocardial ischemia lasting for more than 30 minutes

• Definite ECG changes indicating STEMI

• Patients undergoing primary PCI within 12 hours from symptom onset

• Possibility to perform thrombus aspiration

• Written informed consent

Exclusion Criteria:

• Treatment with fibrinolytic therapy for qualifying index STEMI event

• Patients with known intolerance to aspirin, ticagrelor or heparin

• Patients with active internal bleeding

• Patients with a recent history of intracranial hemorrhage

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Infarction
• MicroRNA
• Myocardial Infarction
• ST Elevation Myocardial Infarction
• STEMI - ST Elevation Myocardial Infarction
• Thrombi
• Thrombosis

Intervention

Procedure:
• thrombus aspiration
Thrombus aspiration will be performed by experienced interventional cardiologists according to standard practices, as previously described. The intracoronary blood samples will be collected as well during the same procedure and- along with peripheral blood samples- they will be analyzed for the presence of specific miRNAs. The aspirated thrombi will be preserved in 10% formalin solution and will be analyzed using the micro/nano-CT scanners.

Locations

Country	Name	City	State
Greece	AHEPA University Hospital	Thessaloníki

Sponsors (4)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	Centre for Research and Technology Hellas, Harvard Medical School (HMS and HSDM), HELLENIC CENTER FOR MARINE RESEARCH

Country where clinical trial is conducted

Greece, 

References & Publications (6)

Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008 Oct;18(10):997-1006. doi: 10.1038/cr.2008.282. — View Citation

Grover SP, Saha P, Jenkins J, Mukkavilli A, Lyons OT, Patel AS, Sunassee K, Modarai B, Smith A. Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography. Thromb Res. 2015 Dec;136(6):1285-90. doi: 10.1016/j.thromres.2015.10.006. Epub 2015 Oct 9. — View Citation

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018 Jan 7;39(2):119-177. doi: 10.1093/eurheartj/ehx393. — View Citation

Navickas R, Gal D, Laucevicius A, Taparauskaite A, Zdanyte M, Holvoet P. Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. Cardiovasc Res. 2016 Sep;111(4):322-37. doi: 10.1093/cvr/cvw174. Epub 2016 Jun 29. Review. — View Citation

Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT, Michalis LK, Serruys PW. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol. 2007 Aug 14;50(7):573-83. Epub 2007 Jul 30. — View Citation

Vorpahl M, Foerst JR, Kelm M, Kaplan AV, Virmani R, Ball T. The complementary role of microCT and histopathology in characterizing the natural history of stented arteries. Expert Rev Cardiovasc Ther. 2011 Jul;9(7):939-48. doi: 10.1586/erc.11.81. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fold changes of differentially-expressed microRNA from peripheral blood from patients suffering from STEMI (measured in log2 scale)	The expression profiles of the total number of microRNAs that exist in the peripheral blood of patients suffering from STEMI will be analyzed using Next Generation Sequencing (NGS). Blood samples collected from the patients will be used to extract microRNAs through the application of suitable microRNA isolation kit (miRNeasy Serum/Plasma kit). Following, the miRNA library construction will be prepared using commercially available reagents (QIAseq miRNA Library kit). The quantification of miRNAs will be done by the Qubit dsDNA HS assay kit in the Qubit fluorometer before the cDNA library generation.Statistical analyses of differentially expressed miRNAs will be carried out using EdgeR by the generalized linear model. Fold changes of differentially-expressed microRNA will be measured in log2 scale.	12 months
Primary	Volume of aspirated thrombus burden	The volume of aspirated thrombi will be quantified (in mm3) using micro-CT.	12 months
Secondary	Association between fold changes of microRNA expression and post-procedural Thrombolysis in Myocardial Infarction (TIMI) flow	Fold changes of differentially-expressed microRNAs (measured in log2 scale as described above) will be correlated to post-procedural TIMI flow (classified as previously described: TIMI flow 0,1,2 or 3).	12 months
Secondary	Association between fold changes of microRNA expression (measured in log2 scale) with distal embolization	Fold changes of differentially-expressed microRNAs (measured in log2 scale, as described above) will be correlated to distal embolization (dichotomous variable-yes/no).	12 months
Secondary	Association between fold changes of microRNAs expression and volume of aspirated thrombus.	Fold changes of differentially-expressed microRNA (measured in log2 scale) will be correlated to the volume of aspirated thrombi (measured in mm3), as it will be quantified using micro-CT.	12 months
Secondary	Association between fold changes of microRNA expression and Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)	Fold changes of differentially-expressed microRNAs (measured in log2 scale) will be correlated to MACCE. MACCE are defined as any of the following: cardiac death, cerebrovascular death, acute myocardial infarction, target lesion revascularization, stent thrombosis or stroke.	12 months