Clinical trial NCT03264859: NGAL and Its Association With the No-reflow Phenomenon in ST-elevation Myocardial Infarction
Official title: Neutrophil Gelatinase-associated Lipocalin (NGAL) and Its Association With the No-reflow Phenomenon in ST-elevation Myocardial Infarction
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: No-Reflow Phenomenon
STEMI - ST Elevation Myocardial Infarction
Keywords: NGAL
STEMI
no-reflow
PCI (Percutaneous Coronary Intervention)
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Zotal Inc.
First posted: 2017-08-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the Sheba Medical Center

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years old presenting with ST-elevation myocardial infarction and undergoing urgent coronary angiography with or without PCI.
* Signed informed consent to participate in the study.

Exclusion Criteria:

* Inability to sign written informed consent.
* Chronic renal failure (eGFR \< 30 ml/min/1.73m2).

Primary outcomes:
measure: No-reflow phenomenon after STEMI
timeFrame: During hospitalization
Secondary outcomes:
measure: In-hospital MACE(major adverse cardiac events)
timeFrame: Average day 5 of hospitalization and before discharge
measure: 30-day MACE
timeFrame: 30-day follow-up
measure: Serial creatinine level
timeFrame: On admission and at fixed time intervals (first 3 hours after admission, 12 hours, 24 hours and every 24 hours or before if indicated)
measure: The need for renal replacement therapy after STEMI
timeFrame: In-hospital (usually 5 days)
measure: Recurrent hospitalization
timeFrame: 30 days
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center, Cardiac Intensive Care Unit
Study officials:
affiliation: Sheba Medical Center
name: Shlomi Matetzky, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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.