Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

LPS and Platelet Activation in Myocardial Infarction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03675789
Recruitment Status : Completed
First Posted : September 18, 2018
Last Update Posted : November 21, 2018
Sponsor:
Collaborator:
Neuromed IRCCS
Information provided by (Responsible Party):
Francesco Violi, University of Roma La Sapienza

Brief Summary:

Platelets play a key role in the athero-thrombotic process. However, the in vivo mechanism accounting for thrombus growth at site of coronary atherosclerotic lesion has not been fully elucidated. While platelet adhesion and aggregation on the thrombogenic core of atherosclerotic plaque is an established mechanism for thrombus growth, the role of systemic factors, which may contribute to thrombus via amplification and propagation of platelet aggregation, is still to be clarified.

There is a growing body of evidence that lipopolysaccharides (LPS), are implicated in athero-thrombosis. Circulating levels of endotoxins have been associated with human atherosclerosis progression, particularly in smokers or in patients with infections. Furthermore, endotoxins seem to be implicated in the thrombotic process through several mechanisms including up-regulation of macrophage tissue factor expression and amplification of platelet response upon interaction with Toll-like receptor 4. The relationship between endotoxins and platelets may be relevant in the context of acute coronary syndromes as endotoxins could locally amplify platelet-derived thrombus growth but this issue is still unexplored.

Previous studies demonstrated that low-grade endotoxemia is detectable in human circulation, likely as consequence of enhanced gut permeability, and may be responsible for leucocyte-platelet aggregate and eventually thrombosis. The investigators hypothesize that low-grade endotoxemia may be observed in patients with coronary heart disease and may favor, at site of coronary unstable plaque, thrombus growth. To explore this issue, Escherichia Coli (EC)-LPS concentration and biomarkers of platelet activation will be measured in coronary thrombus and intra-coronary blood of patients with STEMI and stable angina (SA), respectively, and in peripheral circulation of both patients and controls. EC DNA will be searched in serum of all patients by polymerase chain reaction (PCR). Furthermore, to substantiate that LPS could be biologically active, immune-histochemical analysis of thrombi and in vitro studies will be performed to assess the interplay between LPS and platelet activation.


Condition or disease
Myocardial Infarction Acute Coronary Syndrome

Show Show detailed description

Layout table for study information
Study Type : Observational
Actual Enrollment : 150 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Endotoxemia in Coronary Thrombus of Patients With Acute Coronary Syndrome
Actual Study Start Date : January 2, 2013
Actual Primary Completion Date : July 6, 2018
Actual Study Completion Date : November 5, 2018

Resource links provided by the National Library of Medicine


Group/Cohort
STEMI
50 STEMI patients treated with standard therapy undergoing to primary percutaneous coronary internention (PPCI). Thromboaspiration will be performed whenever possible (when the anatomy of the coronary artery - curve and size- allowed it) in all patients with a TIMI Flow 0 and in all patients with a visible thrombus if TIMI Flow was 1 or more.
Stable angina
50 stable angina (SA) patients on standard therapy, undergoing to intracoronary blood aspiration during elective diagnostic and/or interventional coronary procedure, matched for age, sex and comorbidities with the 50 STEMI patients.
Controls
50 outpatients without coronary heart disease, matched for age gender and comorbidities like diabetes and hypertension with the 50 STEMI patients. Peripheral blood samples will be collected during routine patient monitoring.



Primary Outcome Measures :
  1. LPS in blood of STEMI, SA patients and controls. [ Time Frame: 1 year ]
    LPS will be measured in serum and expressed as concentration (pg/ml)


Secondary Outcome Measures :
  1. LPS in thrombus and intra-coronary blood of STEMI and SA patients. [ Time Frame: 1 year ]
    LPS will be measured in coronary thrombi of STEMI patients and in intra-coronary blood of SA patients and expressed as concentration (pg/ml)

  2. sP-selectin in thrombus and intra-coronary blood of STEMI and SA patients. [ Time Frame: 1 year ]
    sP-selectin (a marker of platelet activation) will be measured in coronary thrombi of STEMI patients and in intra-coronary blood of SA patients and expressed as concentration (ng/ml).

  3. sCD40L in thrombus and intra-coronary blood of STEMI and SA patients. [ Time Frame: 1 year ]
    sCD40L (a marker of platelet activation) will be measured in coronary thrombi of STEMI patients and in intra-coronary blood of SA patients and expressed as concentration (ng/ml).

  4. Escherichia coli-DNA [ Time Frame: 1 year ]
    Escherichia coli-DNA will be searched in serum patients and controls by polymerase chain reaction (PCR).The investigators will evaluate the rate of positivity in the serum of the study population.

  5. Histologic and immunohistochemical analyses of thrombus fragments aspirated from a subset of STEMI patients. [ Time Frame: 1 year ]
    Immunoistochemistry on sections obtained from formalin-fixed and paraffin embedded thrombus fragments.The investigators will analyze the composition of thrombus fragments and the presence of LPS , TLR4 and Cathepsin G.

  6. HS-CRP in blood of STEMI, SA patients and controls [ Time Frame: 1 year ]
    High sensitivity-C reactive protein will be measuer in serum and expressed as concentration (mg/L).

  7. sP-selectin in blood of STEMI, SA patients and controls. [ Time Frame: 1 year ]
    sP-selectin (a marker of platelet activation) will be measured in plasma and expressed as concentration (ng/ml)

  8. Soluble CD40L (sCD40L) in blood of STEMI, SA patients and controls. [ Time Frame: 1 year ]
    sCD40L (a marker of platelet activation) will be measured in plasma and expressed as concentration (ng/ml)

  9. Zonulin in blood of STEMI, SA patients and controls [ Time Frame: 1 year ]
    Zonulin (a marker of gut permeability) will be measued in serum and expressed as concentration (ng/ml)


Biospecimen Retention:   Samples Without DNA
Peripheral blood, aspirated intra-coronary blood, aspirated coronary thrombi, aspirated plaque fragments from coronary culprit lesions.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
  1. STEMI patients referred to the catheterization laboratory for PPCI, who will undergo to manual coronary thrombo-aspiration, that fulfilled the inclusion/exclusion criteria, with a sufficient thrombotic material (≥1 mm3).
  2. patients with chronic stable angina (SA) undergoing elective diagnostic and/or interventional coronary procedure, undergoing to intracoronary blood aspiration
  3. outpatients without coronary heart disease matched for age, gender and comorbidities like diabetes and hypertension
Criteria

Inclusion Criteria:

For STEMI patients:

  • diagnosis of STEMI based on the current European Guidelines

For SA patients:

  • diagnosis of SA defined according to the European Guidelines as lack of episodes of coronary instability for at least 6 months prior to admission

For control subjects:

  • outpatients without diagnosis of coronary heart disease

Exclusion Criteria:

  • estimated glomerular filtration rate less than 30 ml/min/m2
  • acute or recent systemic infections (3 weeks)
  • treatment with systemic corticosteroids
  • treatment with oral anticoagulants
  • malignancy
  • lack of consent to participate

Additional exclusion criteria for STEMI patients were symptoms duration>12 h, rescue PCI, in-stent thrombosis and anatomical difficulty in reaching the lesion.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03675789


Locations
Layout table for location information
Italy
Internal and Medical Specialities Department - Policlinico Umberto I
Rome, Italy, 00162
Sponsors and Collaborators
University of Roma La Sapienza
Neuromed IRCCS
Investigators
Layout table for investigator information
Study Chair: Francesco Violi, MD Sapienza University of Rome
Layout table for additonal information
Responsible Party: Francesco Violi, Director, Head of Internal Medicine, Clinical Professor, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT03675789    
Other Study ID Numbers: EMI-Sapienza
First Posted: September 18, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Francesco Violi, University of Roma La Sapienza:
Thrombi
LPS
Platelet Thrombus
Additional relevant MeSH terms:
Layout table for MeSH terms
Myocardial Infarction
Acute Coronary Syndrome
Syndrome
Infarction
Disease
Pathologic Processes
Ischemia
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases