Pan-Cardio-Genetics Clot Assessment in Acute Coronary Syndromes

NCT03832153 | Withdrawn

• 1 other identifier: 20181028
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

STEMI - ST Elevation Myocardial Infarction; Thrombi; MicroRNA

Keywords

Bioprinting; thrombus aspiration; micro-CT

Outcome Measures

Primary Outcomes (2)

• 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

• Volume of aspirated thrombus burden

  The volume of aspirated thrombi will be quantified (in mm3) using micro-CT.

  12 months

Secondary Outcomes (4)

• Association between fold changes of microRNA expression and post-procedural Thrombolysis in Myocardial Infarction (TIMI) flow

  12 months

• Association between fold changes of microRNA expression (measured in log2 scale) with distal embolization

  12 months

• Association between fold changes of microRNAs expression and volume of aspirated thrombus.

  12 months

• Association between fold changes of microRNA expression and Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)

  12 months

Study Arms (2)

patients with low thrombus burden

patients with the lower volume of aspirated thrombi, as measured using micro-CT

Procedure: thrombus aspiration

patients with high thrombus burden

patients with the higher volume of aspirated thrombi, as measured using micro-CT

Procedure: thrombus aspiration

Interventions

thrombus aspiration PROCEDURE

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.

patients with high thrombus burden; patients with low thrombus burden

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

210 consecutive patients presenting with STEMI and undergoing thrombus aspiration will be enrolled in the study

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• HELLENIC CENTER FOR MARINE RESEARCH: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Centre for Research and Technology Hellas: collaborator

Study Sites (1)

AHEPA University Hospital

Thessaloniki, 54636, Greece

Location

Related Publications (6)

• 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. doi: 10.1016/j.jacc.2007.04.059. Epub 2007 Jul 30.

  PMID: 17692740 BACKGROUND

• 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, Widimsky 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. No abstract available.

  PMID: 28886621 BACKGROUND

• 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.

  PMID: 26489729 BACKGROUND

• 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.

  PMID: 21809975 BACKGROUND

• 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.

  PMID: 18766170 BACKGROUND

• 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.

  PMID: 27357636 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Intracoronary blood samples will be collected (during thrombus aspiration) along with peripheral blood samples and will be analyzed for the presence of specific micro-RNAs. The aspirated thrombi will be preserved in 10% formalin solution and will be analyzed using the Micro/Nano-CT.

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Thrombosis

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Embolism and Thrombosis

Study Officials

• Georgios Sianos

  Associate Professor of Cardiology, Aristotle University of Thessaloniki

  STUDY CHAIR

• Ioannis Vizirianakis

  Associate Professor, School of Pharmacy, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

• Dimitrios Fatouros

  Associate Professor in Pharmaceutical Technology , Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

• Eleftherios Angelis

  Professor in Statistics, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

• Christos Arvanitidis

  Director of Research, Hellenic Center for Marine Research

  PRINCIPAL INVESTIGATOR

• James Michaelson

  Associate Professor, Department of Pathology, Harvard Medical School

  PRINCIPAL INVESTIGATOR

• Athanasios Zacharopoulos

  Post-Doctoral Fellow, Hellenic Center for Marine Research

  PRINCIPAL INVESTIGATOR

• Christos Ouzounis

  Director of Research, Centre for Research and Technology Hellas

  PRINCIPAL INVESTIGATOR

• Efstratios Karagiannidis

  Phd Candidate, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor (resident physician, Cardiology Department, AHEPA University hospital), PhD candidate, Principal Investigator

Study Record Dates

• First Submitted: January 27, 2019
• First Posted: February 6, 2019
• Study Start: January 20, 2019
• Primary Completion: March 30, 2022
• Study Completion: March 30, 2022
• Last Updated: March 3, 2022

Record last verified: 2022-02

Locations

GR (1)