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In this study the investigators test the hypothesis that alteplase given intra coronary after PCI reduce infarct size in patients with ST-elevation myocardial infarction(STEMI) and impaired microvascular function defined as a value of index of microvascular resistance (IMR) >30.
After coronary stenting, index of microvascular resistance (IMR) will be measured invasively. Patients with IMR >30 will be randomised to 20 mg alteplase or placebo (NaCl) administered in the culprit vessel through a microcatheter. Magnet resonance imaging (MRI) of the myocardium will be performed early (2-6 days) and late (3 months) to estimate the primary endpoint (infarct size).
10 non-randomised patients, with IMR <30, will undergo the same follow-up as the randomised patients.
Clinical events for all randomised and non-randomised patients will be collected from Swedish national registries and by telephone at 3 and 12 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alteplase | Experimental | 40 patients: 4-5 minutes of infusion of 10 ml of alteplase 2mg/ml in culprit vessel |
|
| Placebo | Placebo Comparator | 40 patients: 4-5 minutes of infusion of 10 ml of NaCl in culprit vessel |
|
| Observational | No Intervention | 10 patients with IMR <30 will undergo the same follow-up as the randomised patients |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alteplase | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of myocardial infarct size to area at risk assessed by MRI | MRI performed early (day 2-6) to assess area at risk and late (3 months) to assess infarct size | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change of index of microvascular resistance and coronary flow reserve | Difference in invasively measured IMR and CFR before and after drug administration | Immediately after drug administration during invasive index procedure |
| Degree of microvascular obstruction assessed by MRI |
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Criteria for randomization:
1. IMR measured in culprit vessel > 30
Criteria for IMR measurement:
Inclusion Criteria:
Exclusion Criteria:
Previously known ejection fraction <30%
Previous PCI in the culprit vessel
Chronic total occlusion in major vessel
Any history of bleeding diathesis, known coagulopathy, or will refuse blood transfusions
Recent history or known platelet count <100.000 cells/mm3 or Hbg < 10 g/dL
Known reduced kidney function with estimated glomerular filtration rate (GFR) <30 ml/min/1.73m2.
Previous hemorrhagic stroke
Ongoing oral anticoagulation treatment
Severe asthma requiring daily treatment
Any mechanical complication (e.g. ventricular septal defect, papillary muscle rupture, cardiac tamponade)
Atrioventricular block grade III
Known inability to undergo MRI investigation
Permanent pacemaker
Known intolerance to study drug
Known intolerance to adenosine
Pregnancy
Participation in another investigational drug study
Previous randomization in the OPTIMAL-PCI trial
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Oskar Angerås, MD, PhD | Contact | +46703134091 | oskar.angeras@vgregion.se |
| Name | Affiliation | Role |
|---|---|---|
| Oskar Angerås, MD, PhD | Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiology, Sahlgrenska University Hospital | Recruiting | Gothenburg | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18237685 | Background | Fearon WF, Shah M, Ng M, Brinton T, Wilson A, Tremmel JA, Schnittger I, Lee DP, Vagelos RH, Fitzgerald PJ, Yock PG, Yeung AC. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2008 Feb 5;51(5):560-5. doi: 10.1016/j.jacc.2007.08.062. | |
| 19684025 |
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| ID | Term |
|---|---|
| D000072657 | ST Elevation Myocardial Infarction |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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| Drug |
|
|
Degree of microvascular obstruction assessed by MRI |
| 2-6 days |
| Peak level of Troponin T | Peak level of Troponin T | 12 hours |
| Level of NtProBNP | Level of NtProBNP | 12 hours |
| Non invasive CFR | CFR measured with transthoracic echo doppler | 3 months |
| Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | 3 months |
| Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | 12 months |
| Re-hospitalisation for heart failure | Re-hospitalisation for heart failure | 12 months |
| Re-hospitalisation for myocardial infarction | Re-hospitalisation for myocardial infarction | 12 months |
| Cardiovascular death | Cardiovascular death | 12 months |
| Bleeding according to BARC-criteria | Bleeding events during or after index PCI during index hospitalisation | 7 days |
| Myocardial hemorrhage at MRI | Myocardial hemorrhage at MRI | 2-6 days |
| Change in hemoglobin | Change in hemoglobin | 12 hours |
| Lim HS, Yoon MH, Tahk SJ, Yang HM, Choi BJ, Choi SY, Sheen SS, Hwang GS, Kang SJ, Shin JH. Usefulness of the index of microcirculatory resistance for invasively assessing myocardial viability immediately after primary angioplasty for anterior myocardial infarction. Eur Heart J. 2009 Dec;30(23):2854-60. doi: 10.1093/eurheartj/ehp313. Epub 2009 Aug 14. |
| 23681066 | Background | Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, Ho MY, Kim HS, Loh JP, Oldroyd KG. Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation. 2013 Jun 18;127(24):2436-41. doi: 10.1161/CIRCULATIONAHA.112.000298. Epub 2013 May 16. |
| 24637066 | Background | Boscarelli D, Vaquerizo B, Miranda-Guardiola F, Arzamendi D, Tizon H, Sierra G, Delgado G, Fantuzzi A, Estrada D, Garcia-Picart J, Cinca J, Serra A. Intracoronary thrombolysis in patients with ST-segment elevation myocardial infarction presenting with massive intraluminal thrombus and failed aspiration. Eur Heart J Acute Cardiovasc Care. 2014 Sep;3(3):229-36. doi: 10.1177/2048872614527008. Epub 2014 Mar 17. |
| 21670242 | Background | Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available. |
| D014652 |
| Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |