Clinical trial NCT00302419: Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary Percutaneous Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute Myocardial Infarction
Official title: Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary Percutaneous Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Keywords: Acute myocardial infarction
primary angioplasty
streptokinase
microvasculature
Lead sponsor: Istanbul University
Sponsor class: OTHER
First posted: 2006-03-14
Enrollment: 95
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators hypothesized that complementary intracoronary streptokinase administration to primary percutaneous intervention in patients with acute myocardial infarction may provide further improvement in myocardial perfusion by dissolving microvascular thrombus \[in situ formed or embolized from proximal site (spontaneous or following PCI)\] and fibrin.

Detailed description: Mechanical reperfusion for acute myocardial infarction (AMI) targets optimal revascularization of the epicardial artery but also aims at improved myocardial salvage. The goal of reperfusion therapies has shifted to include reperfusion downstream at the level of capillary bed, and it might be more appropriate that the hypothesis now be termed "the time dependent open artery and open microvascular hypothesis." Failure to achieve myocardial reperfusion despite the presence of a patent coronary artery has been termed the "no-reflow" phenomenon and attributed to microvascular dysfunction. It has become apparent that clinical outcomes are not only associated with patency of the epicardial artery, but also with patency of the microcirculation. Persistent impairment of microcirculation is associated with poor clinical outcome. Complete reperfusion in AMI settings necessitates reopening of the all consecutive vascular compartments all the way through the coronary circulation. But, embolization following percutaneous coronary intervention (PCI) and in situ microthrombi generation at the microvascular level makes this goal difficult to achieve. For this reason, mechanical intervention to the epicardial coronary artery with or without using distal protection wouldn't be enough to achieve ideal reperfusion at the ultimate (microvascular) level. At this point, it has become more evident that we need to develop more competent and feasible reperfusion strategies which can help us to achieve reperfusion as complete as possible at all levels.

Hypothesis:

Complementary intracoronary streptokinase administration to primary PCI may provide further improvement in myocardial perfusion by dissolving microvascular thrombus \[in situ formed or embolized from proximal site (spontaneous or following PCI)\] and fibrin. Improvement in microvascular perfusion may translate into reduction in infarct size and improvement in left ventricular function at long term.

Eligibility criteria: Inclusion criteria:

* Continuous chest pain that lasted \> 30 minutes within the preceding 12 hours
* ST-segment elevation of at least 1 mm in 2 contiguous leads on the 12 leads ECG
* Infarct related artery (IRA) occlusion (TIMI grade 0) at the angiography
* Angiographically detected culprit coronary artery lesion deemed suitable for PCI

Exclusion Criteria:

* Contraindications to streptokinase, tirofiban, aspirin, clopidogrel, or heparin
* Culprit lesion in saphenous vein graft
* TIMI grade II-III flow in IRA
* Additional epicardial stenosis in the IRA distal to stented segment (significant or insignificant)
* Presence of left bundle branch block
* History of prior MI
* Mechanical ventilation or inotropic support

Primary outcomes:
measure: Primary end points defined as the indices of the microvascular perfusion which is going to be assessed on day 2 (48 hours after the primary PCI)and infarct size at 6 months.
timeFrame: 6 months
measure: Index of microvascular resistance,
timeFrame: 48 hours
measure: Coronary flow reserve
timeFrame: 48 hours
measure: Left ventricular infarct size by SPECT at six months.
timeFrame: 6 months
Secondary outcomes:
measure: Death
timeFrame: 1 year
measure: Reinfarction
timeFrame: 1 month
measure: Major bleeding
timeFrame: during hospitalization
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istanbul University, Istanbul School of Medicine, Department of Cardiology
Study officials:
affiliation: Istanbul University, Istanbul School of Medicine
name: Murat Sezer, M.D.
role: STUDY_DIRECTOR
affiliation: Istanbul University, Istanbul School of Medicine
name: Sabahattin Umman, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Istanbul University, Istanbul School of Medicine
name: Taner Goren, Prof.
role: STUDY_CHAIR
affiliation: Istanbul University, Istanbul School of Medicine
name: Huseyin Oflaz, Assoc.Prof.
role: STUDY_CHAIR
affiliation: Istanbul University, Istanbul School of Medicine
name: Irem Okcular, M.D.
role: STUDY_CHAIR
affiliation: Istanbul University, Istanbul School of Medicine
name: Yılmaz Nisanci, Prof.
role: STUDY_CHAIR
affiliation: Istanbul University, Istanbul School of Medicine
name: Berrin Umman, Prof.
role: STUDY_CHAIR
affiliation: Istanbul University, Istanbul School of Medicine
name: Ahmet K Bilge, M.D.
role: STUDY_CHAIR
affiliation: Istanbul University, Istanbul School of Medicine
name: Mehmet Meric, Prof.
role: STUDY_CHAIR
References:
citation: Sezer M, Cimen A, Aslanger E, Elitok A, Umman B, Bugra Z, Yormaz E, Turkmen C, Adalet IS, Nisanci Y, Umman S. Effect of intracoronary streptokinase administered immediately after primary percutaneous coronary intervention on long-term left ventricular infarct size, volumes, and function. J Am Coll Cardiol. 2009 Sep 15;54(12):1065-71. doi: 10.1016/j.jacc.2009.04.083.
citation: Sezer M, Oflaz H, Goren T, Okcular I, Umman B, Nisanci Y, Bilge AK, Sanli Y, Meric M, Umman S. Intracoronary streptokinase after primary percutaneous coronary intervention. N Engl J Med. 2007 May 3;356(18):1823-34. doi: 10.1056/NEJMoa054374.