Clinical trial NCT03429608: Quantitative Estimation of Thrombus Burden in Patients With STEMI Using Micro-Computed Tomography (QUEST-STEMI)
Official title: Quantitative Estimation of Thrombus Burden in Patients With ST Elevation Acute Myocardial Infarction (STEMI) With the Use of Micro-computed Tomography-A Methodological Approach (QUEST-STEMI)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ST Elevation Myocardial Infarction
Thrombi
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
Collaborators: name: Hellenic Centre for Marine Research
name: Harvard Medical School (HMS and HSDM)
name: MHAT Hadji Dimitar Hospital, Sliven, Bulgaria
First posted: 2018-02-12
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: consecutive patients presenting with ST elevation myocardial infarction, who undergo primary PCI and thrombus aspiration

Brief summary: The study aims to assess for the first time, through the application of innovative technologies (micro-CT), important characteristics of aspirated thrombi (such as their volume and their density), which might be linked to certain clinical outcomes, in patients presenting with STEMI and referred for primary Percutaneous Coronary Intervention (PCI). To this end, a methodology for the exact estimation of thrombus burden by measuring the volume and the density of aspirated thrombi will be developed. After being aspirated using dedicated catheters, thrombi will be preserved in formalin and their volume and their density will be calculated with the use of micro-CT. Having a better resolution than conventional computed tomography, micro-CT will allow us to create 3D models of aspirated thrombi from a series of x-ray projection images. These 3D models will be further analyzed in order to find the volume and the density of aspirated thrombi. Shape analysis of the surface of aspirated thrombi and potential differences in their structure will also be assessed. Correlation of these variables with clinical parameters and angiographic outcomes will be attempted.

Thus, a risk-stratification model will be developed combining:

* Clinical and laboratory data,
* Angiographic parameters,
* Data regarding the volume, the density and the composition of aspirated thrombi.

This model will enable the stratification of the cardiovascular and cerebrovascular risk of patients and the identification of who will benefit from thrombus aspiration, providing a personalized approach in treating patients with STEMI.

Detailed description: Acute myocardial infarction with ST elevation (STEMI) remains one of the leading causes of mortality in developed countries, in spite of the important advances in pharmacological therapy and in mechanical reperfusion therapy. Having an important role in provoking ischemia, thrombus has been studied in many clinical trials and high thrombus burden has been proven to be an independent risk factor for stent thrombosis and for Major Adverse Clinical outcomes. However large randomized controlled trials concerning thrombus aspiration showed controversial results, providing as a whole no evidence of distinct benefits for thrombus aspiration. A possible explanation could be that aspiration was performed as a routine strategy in all of these trials, whereas these patients should be considered as a heterogeneous group and thus they should be risk-stratified. For this reason, it is of paramount importance to classify patients according to the volume of thrombus burden. The currently existing classifications of thrombus burden (the most important being those of Gibson and of Sianos) are based on visual assessment of angiographic characteristics and thus they are not reflecting the volume of the thrombi in actual, absolute numbers.

The main purpose of the study is to develop a methodology for the exact estimation of thrombus burden by measuring the volume and the density of aspirated thrombi in patients presenting with STEMI and referred for primary PCI. After being aspirated using dedicated catheters, thrombi will be preserved in formalin and their volume will be calculated with the use of micro-CT. The scanning procedure results into a series of projection images arranged in the form of image stacks which, in turn, are reformed in sections (cross section images) with the use of the NRecon (Bruker, Kontich, Belgium) software, which applies a modified algorithm of backward projection Feldkamp. The resulting sections will be combined to create the 3D models which will be further analyzed to extract useful measurements for the characteristics of the thrombi, such as for the volume and the elative density. Shape analysis on the surface and internal structure of the three-dimensional representations of the specimens will lead to the identification of the important features that can be used to estimate variability within samples and perform clustering for the significant differences between clots. In addition, possible differences in clot internal and external structure (e.g. architecture of the various cell types) will be assessed through the 3D models rendered from the stacks of images The Secondary end points of the study include the examination of the association of the aforementioned variables with the angiographic classification of thrombus burden (according to Sianos), with electrocardiographic and angiographic characteristics suggestive of poor patient prognosis and with major adverse cardiac events during the follow-up period of one year.

This method could become the gold standard for the exact measurement of thrombus burden and could be used in larger, clinically-oriented trials to help stratify patients with thrombus burden according to their risk for adverse outcomes.

Eligibility criteria: Inclusion Criteria:

* Patients presenting 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
* Age\>18 years
* Written informed consent prior to enrolment in the clinical trial

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

Primary outcomes:
measure: volume of aspirated thrombus burden
timeFrame: 12 months
measure: density of aspirated thrombus burden
timeFrame: 12 months
measure: MACCE-free survival
timeFrame: 12 months
Secondary outcomes:
measure: association between thrombus volume with factors from patients medical history
timeFrame: 12 months
measure: association between thrombus density with factors from patients medical history
timeFrame: 12 months
measure: Correlation of the volume of aspirated thrombus burden with the Sianos' classification of thrombus burden
timeFrame: 12 months
measure: Correlation of thrombus density with the Sianos' classification of thrombus burden
timeFrame: 12 months
measure: association of thrombus volume with electrocardiographic outcomes suggestive of poor patient prognosis
timeFrame: 12 months
measure: association of thrombus density with electrocardiographic outcomes suggestive of poor patient prognosis
timeFrame: 12 months
measure: association of thrombus volume with post-procedural Thrombolysis in Myocardial Infarction(TIMI) flow
timeFrame: 12 months
measure: association of thrombus density with post-procedural TIMI flow
timeFrame: 12 months
measure: association of thrombus volume with myocardial blush grade
timeFrame: 12 months
measure: association of thrombus density with myocardial blush grade
timeFrame: 12 months
measure: association of thrombus volume with distal embolization .
timeFrame: 12 months
measure: association of thrombus density with distal embolization .
timeFrame: 12 months
measure: association of thrombus volume with Major Adverse Cardiac and Cerebrovascular Events (MACCE)
timeFrame: 12 months
measure: association of thrombus density with Major Adverse Cardiac and Cerebrovascular Events (MACCE)
timeFrame: 12 months
Other outcomes:
Locations:
city: Thessaloníki
country: Greece
facility: University General Hospital of Thessaloniki AHEPA
Study officials:
affiliation: Associate Professor of Cardiology, School of Medicine, Aristotle University of Thessaloniki
name: Georgios Sianos, MD,PhD, FESC
role: STUDY_CHAIR
affiliation: Phd candidate, Aristotle University of Thessaloniki
name: Efstratios Karagiannidis, MD,MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of Cardiology, School of Medicine, Aristotle University of Thessaloniki
name: Charalambos Karvounis, MD,Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistant Professor of Cardiology, School of Medicine, Aristotle University of Thessaloniki
name: George Giannakoulas, MD,Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: Director of Research, Hellenic Center for Marine Research
name: Christos Arvanitidis, Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor, School of Pharmacy, Aristotle University of Thessaloniki
name: Ioannis Vizirianakis, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor, Department of Pathology, Harvard Medical School
name: James S Michaelson, MD,Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: HELLENIC CENTER FOR MARINE RESEARCH
name: Kleoniki Keklikoglou, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of cardiology department at MHAT"Hadzy Dimityr" Sliven
name: Ivelin Samra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Phd candidate, Aristotle University of Thessaloniki
name: Nikolaos Konstantinidis, MD,MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aristotle University Of Thessaloniki
name: Georgios Sofidis, MD,Phd
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/j.jacc.2007.04.059. Epub 2007 Jul 30.
citation: Sianos G, Papafaklis MI, Serruys PW. Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J Invasive Cardiol. 2010 Oct;22(10 Suppl B):6B-14B.
citation: Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E; TIMI Study Group. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation. 2001 May 29;103(21):2550-4. doi: 10.1161/01.cir.103.21.2550.
citation: Elgendy IY, Huo T, Bhatt DL, Bavry AA. Is Aspiration Thrombectomy Beneficial in Patients Undergoing Primary Percutaneous Coronary Intervention? Meta-Analysis of Randomized Trials. Circ Cardiovasc Interv. 2015 Jul;8(7):e002258. doi: 10.1161/CIRCINTERVENTIONS.114.002258.
citation: Karagiannidis E, Papazoglou AS, Sofidis G, Chatzinikolaou E, Keklikoglou K, Panteris E, Kartas A, Stalikas N, Zegkos T, Girtovitis F, Moysidis DV, Stefanopoulos L, Koupidis K, Hadjimiltiades S, Giannakoulas G, Arvanitidis C, Michaelson JS, Karvounis H, Sianos G. Micro-CT-Based Quantification of Extracted Thrombus Burden Characteristics and Association With Angiographic Outcomes in Patients With ST-Elevation Myocardial Infarction: The QUEST-STEMI Study. Front Cardiovasc Med. 2021 Apr 21;8:646064. doi: 10.3389/fcvm.2021.646064. eCollection 2021.
citation: Karagiannidis E, Konstantinidis NV, Sofidis G, Chatzinikolaou E, Sianos G. Rationale and design of a prospective, observational study for the QUantitative EStimation of Thrombus burden in patients with ST-Elevation Myocardial Infarction using micro-computed tomography: the QUEST-STEMI trial. BMC Cardiovasc Disord. 2020 Mar 11;20(1):125. doi: 10.1186/s12872-020-01393-5.