Clinical trial NCT02894138: Optimal Coronary Flow After PCI for Myocardial Infarction - a Pilot Study
Official title: Optimal Coronary Flow After PCI for Myocardial Infarction - a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: ST-segment Elevation Myocardial Infarction
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2016-09-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) \>30.

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.

Eligibility criteria: Criteria for randomization:

1. IMR measured in culprit vessel \> 30

Criteria for IMR measurement:

Inclusion Criteria:

1. Oral and signed informed consent
2. Males and females 18 - 85 years of age
3. Diagnosis of ST-elevation myocardial infarction (STEMI) including occlusion of culprit vessel on angiography
4. Onset of continuous symptoms within 12 hours
5. Have undergone PCI of culprit vessel
6. Subjects are willing to comply with scheduled visits and tests and are able and willing to provide informed consent

Exclusion Criteria:

1. Previously known ejection fraction \<30%
2. Previous PCI in the culprit vessel
3. Chronic total occlusion in major vessel
4. Any history of bleeding diathesis, known coagulopathy, or will refuse blood transfusions
5. Recent history or known platelet count \<100.000 cells/mm3 or Hbg \< 10 g/dL
6. Known reduced kidney function with estimated glomerular filtration rate (GFR) \<30 ml/min/1.73m2.
7. Previous hemorrhagic stroke
8. Ongoing oral anticoagulation treatment
9. Severe asthma requiring daily treatment
10. Any mechanical complication (e.g. ventricular septal defect, papillary muscle rupture, cardiac tamponade)
11. Atrioventricular block grade III
12. Known inability to undergo MRI investigation

    Permanent pacemaker
    * Pronounced claustrophobia
13. Known intolerance to study drug
14. Known intolerance to adenosine
15. Pregnancy
16. Participation in another investigational drug study
17. Previous randomization in the OPTIMAL-PCI trial

Primary outcomes:
measure: Ratio of myocardial infarct size to area at risk assessed by MRI
timeFrame: 3 months
Secondary outcomes:
measure: Change of index of microvascular resistance and coronary flow reserve
timeFrame: Immediately after drug administration during invasive index procedure
measure: Degree of microvascular obstruction assessed by MRI
timeFrame: 2-6 days
measure: Peak level of Troponin T
timeFrame: 12 hours
measure: Level of NtProBNP
timeFrame: 12 hours
measure: Non invasive CFR
timeFrame: 3 months
measure: Major adverse cardiac event (myocardial infarction, stroke, heart failure or death)
timeFrame: 3 months
measure: Major adverse cardiac event (myocardial infarction, stroke, heart failure or death)
timeFrame: 12 months
measure: Re-hospitalisation for heart failure
timeFrame: 12 months
measure: Re-hospitalisation for myocardial infarction
timeFrame: 12 months
measure: Cardiovascular death
timeFrame: 12 months
measure: Bleeding according to BARC-criteria
timeFrame: 7 days
measure: Myocardial hemorrhage at MRI
timeFrame: 2-6 days
measure: Change in hemoglobin
timeFrame: 12 hours
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Cardiology, Sahlgrenska University Hospital
Study officials:
affiliation: Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
name: Oskar Angerås, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.