OPTIMAL: Optimal Coronary Flow After PCI for Myocardial Infarction - a Pilot Study
Study Details
Study Description
Brief Summary
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Alteplase 40 patients: 4-5 minutes of infusion of 10 ml of alteplase 2mg/ml in culprit vessel |
Drug: alteplase
Other Names:
|
| Placebo Comparator: Placebo 40 patients: 4-5 minutes of infusion of 10 ml of NaCl in culprit vessel |
Drug: Placebo
Other Names:
|
| No Intervention: Observational 10 patients with IMR <30 will undergo the same follow-up as the randomised patients |
Outcome Measures
Primary Outcome Measures
- Ratio of myocardial infarct size to area at risk assessed by MRI [3 months]
MRI performed early (day 2-6) to assess area at risk and late (3 months) to assess infarct size
Secondary Outcome Measures
- Change of index of microvascular resistance and coronary flow reserve [Immediately after drug administration during invasive index procedure]
Difference in invasively measured IMR and CFR before and after drug administration
- Degree of microvascular obstruction assessed by MRI [2-6 days]
Degree of microvascular obstruction assessed by MRI
- Peak level of Troponin T [12 hours]
Peak level of Troponin T
- Level of NtProBNP [12 hours]
Level of NtProBNP
- Non invasive CFR [3 months]
CFR measured with transthoracic echo doppler
- 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]
Major adverse cardiac event (myocardial infarction, stroke, heart failure or death)
- Re-hospitalisation for heart failure [12 months]
Re-hospitalisation for heart failure
- Re-hospitalisation for myocardial infarction [12 months]
Re-hospitalisation for myocardial infarction
- Cardiovascular death [12 months]
Cardiovascular death
- Bleeding according to BARC-criteria [7 days]
Bleeding events during or after index PCI during index hospitalisation
- Myocardial hemorrhage at MRI [2-6 days]
Myocardial hemorrhage at MRI
- Change in hemoglobin [12 hours]
Change in hemoglobin
Eligibility Criteria
Criteria
Criteria for randomization:
- IMR measured in culprit vessel > 30
Criteria for IMR measurement:
Inclusion Criteria:
-
Oral and signed informed consent
-
Males and females 18 - 85 years of age
-
Diagnosis of ST-elevation myocardial infarction (STEMI) including occlusion of culprit vessel on angiography
-
Onset of continuous symptoms within 12 hours
-
Have undergone PCI of culprit vessel
-
Subjects are willing to comply with scheduled visits and tests and are able and willing to provide informed consent
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
- Pronounced claustrophobia
-
Known intolerance to study drug
-
Known intolerance to adenosine
-
Pregnancy
-
Participation in another investigational drug study
-
Previous randomization in the OPTIMAL-PCI trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Cardiology, Sahlgrenska University Hospital | Gothenburg | Sweden |
Sponsors and Collaborators
- Vastra Gotaland Region
Investigators
- Principal Investigator: Oskar Angerås, MD, PhD, Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- OPTIMAL-01