<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03264859</url>
  </required_header>
  <id_info>
    <org_study_id>SHEBA-17-4157-SM-CTIL</org_study_id>
    <nct_id>NCT03264859</nct_id>
  </id_info>
  <brief_title>NGAL and Its Association With the No-reflow Phenomenon in ST-elevation Myocardial Infarction</brief_title>
  <official_title>Neutrophil Gelatinase-associated Lipocalin (NGAL) and Its Association With the No-reflow Phenomenon in ST-elevation Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheba Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zotal Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sheba Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to investigate the association between NGAL plasma levels in&#xD;
      ST-elevation myocardial infarction and the no-reflow phenomenon, adverse events during&#xD;
      hospitalization and at 30-day follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neutrophil Gelatinase-associated Lipocalin (NGAL) is a acute phase protein which is elevated&#xD;
      in conditions like acute kidney injury and myocardial infarction. When a coronary artery is&#xD;
      occluded, detrimental changes occur in myocardial vessels. After relief of the occlusion,&#xD;
      blood flow to the heart may still be impeded, a phenomenon known as &quot;no-reflow&quot;. Data is&#xD;
      lacking on factors associated with early detection of patients at risk for this phenomenon,&#xD;
      and early stratification of this group seems vital since the no-reflow phenomenon is&#xD;
      associated with worse outcomes. The investigators hypothesized that there might be an&#xD;
      association between higher NGAL levels and the occurrence of no-flow findings, and that NGAL&#xD;
      might serve as a marker of worse prognosis in this population. The investigators also&#xD;
      hypothesized that NGAL levels might serve as a marker of early acute kidney injury and that&#xD;
      there might be specific patterns of NGAL levels over time in different subsets of patients.&#xD;
      The aim of the study is to determine the association between NGAL levels at admission and&#xD;
      during the first days after a ST-elevation myocardial infarction, the occurrence of the&#xD;
      no-reflow phenomenon, the extent of myocardial damage ascertained by cardiac imaging&#xD;
      techniques (echocardiography and cardiac resonance imaging). Data regarding patients'&#xD;
      clinical, laboratory, electrocardiogram, coronary angiography and percutaneous coronary&#xD;
      intervention, in-hospital and 30-day follow-up after discharge will be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 15, 2017</start_date>
  <completion_date type="Anticipated">October 31, 2018</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>No-reflow phenomenon after STEMI</measure>
    <time_frame>During hospitalization</time_frame>
    <description>No-reflow phenomenon as defined by electrocardiographic, angiographic and cardiac magnetic resonance imaging criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-hospital MACE(major adverse cardiac events)</measure>
    <time_frame>Average day 5 of hospitalization and before discharge</time_frame>
    <description>In-hospital MACE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day MACE</measure>
    <time_frame>30-day follow-up</time_frame>
    <description>30-day MACE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serial creatinine level</measure>
    <time_frame>On admission and at fixed time intervals (first 3 hours after admission, 12 hours, 24 hours and every 24 hours or before if indicated)</time_frame>
    <description>Creatinine levels as a maker of acute kidney injury reported in mg/dl</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The need for renal replacement therapy after STEMI</measure>
    <time_frame>In-hospital (usually 5 days)</time_frame>
    <description>Patients started on hemodyalisis due to acute kidney injury during the index hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrent hospitalization</measure>
    <time_frame>30 days</time_frame>
    <description>Recurrent hospitalization at 30 days after the index hospitalization</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>No-Reflow Phenomenon</condition>
  <condition>STEMI - ST Elevation Myocardial Infarction</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>NGAL levels early and post STEMI</intervention_name>
    <description>NGAL levels early and post ST elevation MI (STEMI)</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients admitted to the Sheba Medical Center&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt; 18 years old presenting with ST-elevation myocardial infarction and&#xD;
             undergoing urgent coronary angiography with or without PCI.&#xD;
&#xD;
          -  Signed informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to sign written informed consent.&#xD;
&#xD;
          -  Chronic renal failure (eGFR &lt; 30 ml/min/1.73m2).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shlomi Matetzky, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheba Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fernando Chernomordik, M.D.</last_name>
    <phone>+972-3-5302504</phone>
    <email>fernando.chernomordik@sheba.health.gov.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sheba Medical Center, Cardiac Intensive Care Unit</name>
      <address>
        <city>Ramat Gan</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993 May 15;268(14):10425-32.</citation>
    <PMID>7683678</PMID>
  </reference>
  <reference>
    <citation>Xu SY, Carlson M, Engstrom A, Garcia R, Peterson CG, Venge P. Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. Scand J Clin Lab Invest. 1994 Aug;54(5):365-76. doi: 10.3109/00365519409088436.</citation>
    <PMID>7997842</PMID>
  </reference>
  <reference>
    <citation>Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005 Apr 2-8;365(9466):1231-8. doi: 10.1016/S0140-6736(05)74811-X.</citation>
    <PMID>15811456</PMID>
  </reference>
  <reference>
    <citation>Leclercq A, Houard X, Philippe M, Ollivier V, Sebbag U, Meilhac O, Michel JB. Involvement of intraplaque hemorrhage in atherothrombosis evolution via neutrophil protease enrichment. J Leukoc Biol. 2007 Dec;82(6):1420-9. doi: 10.1189/jlb.1106671. Epub 2007 Sep 7.</citation>
    <PMID>17827339</PMID>
  </reference>
  <reference>
    <citation>Zografos T, Haliassos A, Korovesis S, Giazitzoglou E, Voridis E, Katritsis D. Association of neutrophil gelatinase-associated lipocalin with the severity of coronary artery disease. Am J Cardiol. 2009 Oct 1;104(7):917-20. doi: 10.1016/j.amjcard.2009.05.023.</citation>
    <PMID>19766756</PMID>
  </reference>
  <reference>
    <citation>Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006 Sep;105(3):485-91. doi: 10.1097/00000542-200609000-00011.</citation>
    <PMID>16931980</PMID>
  </reference>
  <reference>
    <citation>Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil-gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol. 2006;26(3):287-92. doi: 10.1159/000093961. Epub 2006 Jun 13.</citation>
    <PMID>16772710</PMID>
  </reference>
  <reference>
    <citation>Lindberg S, Jensen JS, Hoffmann S, Iversen AZ, Pedersen SH, Biering-Sorensen T, Galatius S, Flyvbjerg A, Mogelvang R, Magnusson NE. Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction. Cardiorenal Med. 2016 May;6(3):180-90. doi: 10.1159/000443846. Epub 2016 Feb 25.</citation>
    <PMID>27275154</PMID>
  </reference>
  <reference>
    <citation>Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H, Matsui H, Toki Y, Ito T, Hayakawa T. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol. 2000 Oct;36(4):1202-9. doi: 10.1016/s0735-1097(00)00865-2.</citation>
    <PMID>11028471</PMID>
  </reference>
  <reference>
    <citation>Aksan G, Soylu K, Aksoy O, Ozdemir M, Yanik A, Yuksel S, Gedikli O, Gulel O, Sahin M. The relationship between neutrophil gelatinase-associated lipocalin levels and the slow coronary flow phenomenon. Coron Artery Dis. 2014 Sep;25(6):505-9. doi: 10.1097/MCA.0000000000000121.</citation>
    <PMID>24801557</PMID>
  </reference>
  <reference>
    <citation>Helanova K, Littnerova S, Kubena P, Ganovska E, Pavlusova M, Kubkova L, Jarkovsky J, Pavkova Goldbergova M, Lipkova J, Gottwaldova J, Kala P, Toman O, Dastych M, Spinar J, Parenica J. Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study. BMJ Open. 2015 Oct 5;5(10):e006872. doi: 10.1136/bmjopen-2014-006872.</citation>
    <PMID>26438132</PMID>
  </reference>
  <reference>
    <citation>Akcay AB, Ozlu MF, Sen N, Cay S, Ozturk OH, Yalcn F, Bilen P, Kanat S, Karakas MF, Isleyen A, Demir AD, Sogut S, Covic A, Kanbay M. Prognostic significance of neutrophil gelatinase-associated lipocalin in ST-segment elevation myocardial infarction. J Investig Med. 2012 Feb;60(2):508-13. doi: 10.2310/JIM.0b013e31823e9d86.</citation>
    <PMID>22222228</PMID>
  </reference>
  <reference>
    <citation>Durante A, Laricchia A, Benedetti G, Esposito A, Margonato A, Rimoldi O, De Cobelli F, Colombo A, Camici PG. Identification of High-Risk Patients After ST-Segment-Elevation Myocardial Infarction: Comparison Between Angiographic and Magnetic Resonance Parameters. Circ Cardiovasc Imaging. 2017 Jun;10(6):e005841. doi: 10.1161/CIRCIMAGING.116.005841.</citation>
    <PMID>28592591</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>August 28, 2017</last_update_submitted>
  <last_update_submitted_qc>August 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sheba Medical Center</investigator_affiliation>
    <investigator_full_name>Dr. Shlomi Matetzky</investigator_full_name>
    <investigator_title>Head, Intensive Care Care Unit</investigator_title>
  </responsible_party>
  <keyword>NGAL</keyword>
  <keyword>STEMI</keyword>
  <keyword>no-reflow</keyword>
  <keyword>PCI (Percutaneous Coronary Intervention)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
    <mesh_term>No-Reflow Phenomenon</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03264859
org study id: SHEBA-17-4157-SM-CTIL
nct id: NCT03264859
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to investigate the association between NGAL plasma levels in
      ST-elevation myocardial infarction and the no-reflow phenomenon, adverse events during
      hospitalization and at 30-day follow-up.
Neutrophil Gelatinase-associated Lipocalin (NGAL) is a acute phase protein which is elevated
      in conditions like acute kidney injury and myocardial infarction. When a coronary artery is
      occluded, detrimental changes occur in myocardial vessels. After relief of the occlusion,
      blood flow to the heart may still be impeded, a phenomenon known as "no-reflow". Data is
      lacking on factors associated with early detection of patients at risk for this phenomenon,
      and early stratification of this group seems vital since the no-reflow phenomenon is
      associated with worse outcomes. The investigators hypothesized that there might be an
      association between higher NGAL levels and the occurrence of no-flow findings, and that NGAL
      might serve as a marker of worse prognosis in this population. The investigators also
      hypothesized that NGAL levels might serve as a marker of early acute kidney injury and that
      there might be specific patterns of NGAL levels over time in different subsets of patients.
      The aim of the study is to determine the association between NGAL levels at admission and
      during the first days after a ST-elevation myocardial infarction, the occurrence of the
      no-reflow phenomenon, the extent of myocardial damage ascertained by cardiac imaging
      techniques (echocardiography and cardiac resonance imaging). Data regarding patients'
      clinical, laboratory, electrocardiogram, coronary angiography and percutaneous coronary
      intervention, in-hospital and 30-day follow-up after discharge will be recorded.
observational model: Cohort
time perspective: Prospective
measure: No-reflow phenomenon after STEMI
time frame: During hospitalization
description: No-reflow phenomenon as defined by electrocardiographic, angiographic and cardiac magnetic resonance imaging criteria.
measure: In-hospital MACE(major adverse cardiac events)
time frame: Average day 5 of hospitalization and before discharge
description: In-hospital MACE
measure: 30-day MACE
time frame: 30-day follow-up
description: 30-day MACE
measure: Serial creatinine level
time frame: On admission and at fixed time intervals (first 3 hours after admission, 12 hours, 24 hours and every 24 hours or before if indicated)
description: Creatinine levels as a maker of acute kidney injury reported in mg/dl
measure: The need for renal replacement therapy after STEMI
time frame: In-hospital (usually 5 days)
description: Patients started on hemodyalisis due to acute kidney injury during the index hospitalization
measure: Recurrent hospitalization
time frame: 30 days
description: Recurrent hospitalization at 30 days after the index hospitalization
intervention type: Diagnostic Test
intervention name: NGAL levels early and post STEMI
description: NGAL levels early and post ST elevation MI (STEMI)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shlomi Matetzky, Prof.
role: Principal Investigator
affiliation: Sheba Medical Center
last name: Fernando Chernomordik, M.D.
phone: +972-3-5302504
email: fernando.chernomordik@sheba.health.gov.il
facility: 
country: Israel
citation: Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993 May 15;268(14):10425-32.
PMID: 7683678
citation: Xu SY, Carlson M, Engstrom A, Garcia R, Peterson CG, Venge P. Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. Scand J Clin Lab Invest. 1994 Aug;54(5):365-76. doi: 10.3109/00365519409088436.
PMID: 7997842
citation: Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005 Apr 2-8;365(9466):1231-8. doi: 10.1016/S0140-6736(05)74811-X.
PMID: 15811456
citation: Leclercq A, Houard X, Philippe M, Ollivier V, Sebbag U, Meilhac O, Michel JB. Involvement of intraplaque hemorrhage in atherothrombosis evolution via neutrophil protease enrichment. J Leukoc Biol. 2007 Dec;82(6):1420-9. doi: 10.1189/jlb.1106671. Epub 2007 Sep 7.
PMID: 17827339
citation: Zografos T, Haliassos A, Korovesis S, Giazitzoglou E, Voridis E, Katritsis D. Association of neutrophil gelatinase-associated lipocalin with the severity of coronary artery disease. Am J Cardiol. 2009 Oct 1;104(7):917-20. doi: 10.1016/j.amjcard.2009.05.023.
PMID: 19766756
citation: Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006 Sep;105(3):485-91. doi: 10.1097/00000542-200609000-00011.
PMID: 16931980
citation: Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil-gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol. 2006;26(3):287-92. doi: 10.1159/000093961. Epub 2006 Jun 13.
PMID: 16772710
citation: Lindberg S, Jensen JS, Hoffmann S, Iversen AZ, Pedersen SH, Biering-Sorensen T, Galatius S, Flyvbjerg A, Mogelvang R, Magnusson NE. Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction. Cardiorenal Med. 2016 May;6(3):180-90. doi: 10.1159/000443846. Epub 2016 Feb 25.
PMID: 27275154
citation: Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H, Matsui H, Toki Y, Ito T, Hayakawa T. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol. 2000 Oct;36(4):1202-9. doi: 10.1016/s0735-1097(00)00865-2.
PMID: 11028471
citation: Aksan G, Soylu K, Aksoy O, Ozdemir M, Yanik A, Yuksel S, Gedikli O, Gulel O, Sahin M. The relationship between neutrophil gelatinase-associated lipocalin levels and the slow coronary flow phenomenon. Coron Artery Dis. 2014 Sep;25(6):505-9. doi: 10.1097/MCA.0000000000000121.
PMID: 24801557
citation: Helanova K, Littnerova S, Kubena P, Ganovska E, Pavlusova M, Kubkova L, Jarkovsky J, Pavkova Goldbergova M, Lipkova J, Gottwaldova J, Kala P, Toman O, Dastych M, Spinar J, Parenica J. Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study. BMJ Open. 2015 Oct 5;5(10):e006872. doi: 10.1136/bmjopen-2014-006872.
PMID: 26438132
citation: Akcay AB, Ozlu MF, Sen N, Cay S, Ozturk OH, Yalcn F, Bilen P, Kanat S, Karakas MF, Isleyen A, Demir AD, Sogut S, Covic A, Kanbay M. Prognostic significance of neutrophil gelatinase-associated lipocalin in ST-segment elevation myocardial infarction. J Investig Med. 2012 Feb;60(2):508-13. doi: 10.2310/JIM.0b013e31823e9d86.
PMID: 22222228
citation: Durante A, Laricchia A, Benedetti G, Esposito A, Margonato A, Rimoldi O, De Cobelli F, Colombo A, Camici PG. Identification of High-Risk Patients After ST-Segment-Elevation Myocardial Infarction: Comparison Between Angiographic and Magnetic Resonance Parameters. Circ Cardiovasc Imaging. 2017 Jun;10(6):e005841. doi: 10.1161/CIRCIMAGING.116.005841.
PMID: 28592591
responsible party type: Principal Investigator
investigator affiliation: Sheba Medical Center
investigator full name: Dr. Shlomi Matetzky
investigator title: Head, Intensive Care Care Unit
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: No-Reflow Phenomenon
sharing ipd: No