Minimal Invasive Procedure for Myocardial Infarction

ST Elevation Myocardial Infarction Clinical Trial

— MIMI  

Official title:

Patients Presenting With Acute STEMI Treated With Primary PCI : Comparison of the Impact of the MIMI Approach With a Conventional Strategy of Immediate Stenting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01360242
• Other study ID #: 2010-A01345-34
• Status: Completed
• Phase: Phase 3
• First received: April 28, 2011
• Last updated: March 5, 2015
• Start date: June 2011
• Est. completion date: June 2013

Study information

• Verified date: March 2015
• Source: Centre Hospitalier de la Région d'Annecy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the setting of primary Percutaneous Coronary Intervention (PCI), the investigators hypothesize that a 24-48 hour delay strategy of stenting after successful thrombus aspiration and establishment of Thrombolysis In Myocardial Infarction (TIMI)-3 flow with optimal antithrombotic therapy may decrease the risk of MicroVascular Obstruction (MVO) as assessed by Cardiac Magnetic Resonance Imaging (CMRI).

Description:

Primary PCI is the reperfusion therapy of choice in patients with acute ST-elevation myocardial infarction (STEMI) [Van de Werf et al. 2008; Kushner et al. 2009]. The first objective in primary PCI is to restore TIMI-3 flow. However, despite restoration of TIMI-3 flow, myocardial reperfusion remains suboptimal in a significant proportion of patients, predominantly as a consequence of the so called "myocardial non-reperfusion phenomenon", "low/no-reflow phenomenon" or MVO. This, in turn, is associated with significant morbidity and mortality [Brodie et al. 2005; Bruder et al. 2008; Hombach et al. 2005; Nijveldt et al. 2008; Thiele et al. 2008; Wu et al. 1998]. Although TIMI flow is well assessed by angiography, contrast-enhanced CMRI remains the gold standard in the assessment of MVO. Indeed, the presence and extent of hypoenhanced areas have been shown to be associated with a poor outcome [Bruder et al. 2008; Hombach et al. 2005; Nijveldt et al. 2008; Wu et al. 1998].

There is now a large body of evidence to suggest that even in patients with TIMI-3 flow on angiography, as many as 60% of these patients will subsequently exhibit MVO with CMRI [Brodie et al. 2005; Bruder et al. 2008; Hombach et al. 2005; Nijveldt et al. 2008; Thiele et al. 2008; Wu et al. 1998]. Our knowledge of the mechanisms of MVO occurrence as well as measures to reduce MVO has been considerably enhanced by recent publications. For instance, Sianos et al. [2007] demonstrated that the thrombus burden at the time of angiography is an independent predictor of MVO extension and 2-year mortality. Furthermore, Isaaz et al. [2006] recommended a two-step strategy as a means of minimising the risk of MVO, with the first step consisting of TIMI-3 flow restoration, followed 2-6 days later by further angiography to determine the therapeutic strategy of choice (PCI, cardiac surgery, or medical treatment: 67%, 25%, and 8% respectively). Meneveau et al. [2009] also adopted a two-step strategy in a small cohort of STEMI patients with TIMI-3 flow and ST-segment regression at the time of the procedure. They demonstrated that a 24-hour delay in stent implantation led to a higher rate of procedural success than immediate stenting. Isaaz et al. [2006] and Meneveau et al. [2009] also reported a decreased thrombus burden and no culprit-artery re-occlusion between the first and the second procedure.

Both the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) [Svilaas et al. 2008] and the thrombectomy with EXPort catheter in Infarct-Related Artery during primary percutaneous coronary intervention (EXPIRA) [Sardella et al. 2009] studies demonstrated the benefits of thrombus aspiration as the first step in primary PCI prior to either ballooning or direct stenting. However, as the effects of stenting upon MVO in the setting of acute STEMI remain poorly understood, we propose a randomized study to evaluate the benefits of a 24-48-hour delay in stent implantation compared to immediate stenting in patients presenting with acute STEMI who will undergo primary PCI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with acute STEMI presenting within 12 hours of symptom onset, requiring a primary percutaneous coronary intervention; and written informed consent.

• Patients will be randomized during the angiography if the initial TIMI flow is 0 or 1 in a major artery and if TIMI-3 flow can be restored after thrombus aspiration and sustained for 10 minutes.

• Acute STEMI is defined as typical chest pain with 30 minutes of sustained ST-segment elevation >1 mm in two or more consecutive limb leads or >2 mm in two or more precordial leads in the ECG. Major artery is defined as the proximal or mid segment of the left descending artery, the proximal segment of the circumflex artery (before the first marginal), or the right coronary artery before the posterior descendant artery.

Exclusion Criteria:

• Patients less than 18 years' old

• Pregnant and breast feeding women

• Patients with a pacemaker, automated implantable cardioverter-defibrillator (AICD), or left bundle branch block

• Contraindication to abciximab, prasugrel, or clopidogrel

• Cardiac arrest as initial presentation

• Current medical condition with a life expectancy of < 6 months

• Patients not living in France

• Patients in cardiogenic shock

• Culprit artery <2.5 mm

• Absence of informed consent

• Patients with initial TIMI 2 or 3 flow or no TIMI-3 flow restored after thrombus aspiration

• Rescue PCI after fibrinolysis

• Known creatinine clearance < 30 ml/min.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Procedure:
• MIMI procedure (two-step strategy)
A second coronary angiogram is performed 24-48 hours later and the physician is free to decide on the best treatment, i.e. surgery, medical treatment, or stent implantation (drug-eluting stent if indicated for on-label patients). If stenting is required and the thrombus is still too large (greater than twice the artery width), the physician could postpone stent implantation for days or weeks.
• Immediate Stenting (one-step strategy)
The physician is encouraged to implant a stent after the thrombus aspiration (drug-eluting stent if indicated for on-label patients).

Locations

Country	Name	City	State
France	CHRA	Annecy
France	Hopital Privé	Antony
France	Ch Bastia	Bastia
France	Clinique Convert	Bourg En Bresse
France	CH	Cannes
France	CH	Chambery
France	CHU	Clermont Ferrand
France	CHU	Dijon
France	CHU Nord	Grenoble
France	Clinique Mutualiste	Grenoble
France	CHU	Lille
France	CH St Luc St Joseph	Lyon
France	CHU Croix Rousse	Lyon
France	Clinique du Tonkin	Lyon
France	CHU Nord	Marseille
France	CHI	Montfermeil
France	Clinique Marie Lannelongue	Paris
France	CH	Pontoise
France	Clinique de Courlancy	Reims
France	Clinique St Hilaire	Rouen
France	CHU	St Etienne
France	Clinique St Gatien	Tours
France	CH	Valence
France	CH	Vichy

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier de la Région d'Annecy	University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (14)

Bovill EG, Terrin ML, Stump DC, Berke AD, Frederick M, Collen D, Feit F, Gore JM, Hillis LD, Lambrew CT, et al. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. Ann Intern Med. 1991 Aug 15;115(4):256-65. — View Citation

Brodie BR, Stuckey TD, Hansen C, VerSteeg DS, Muncy DB, Moore S, Gupta N, Downey WE. Relation between electrocardiographic ST-segment resolution and early and late outcomes after primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol. 2005 Feb 1;95(3):343-8. — View Citation

Bruder O, Breuckmann F, Jensen C, Jochims M, Naber CK, Barkhausen J, Erbel R, Sabin GV; Herzinfarktverbund Essen. Prognostic impact of contrast-enhanced CMR early after acute ST segment elevation myocardial infarction (STEMI) in a regional STEMI network: results of the "Herzinfarktverbund Essen". Herz. 2008 Mar;33(2):136-42. doi: 10.1007/s00059-008-3102-8. — View Citation

Hombach V, Grebe O, Merkle N, Waldenmaier S, Höher M, Kochs M, Wöhrle J, Kestler HA. Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J. 2005 Mar;26(6):549-57. Epub 2005 Feb 15. — View Citation

Isaaz K, Robin C, Cerisier A, Lamaud M, Richard L, Da Costa A, Sabry MH, Gerenton C, Blanc JL. A new approach of primary angioplasty for ST-elevation acute myocardial infarction based on minimalist immediate mechanical intervention. Coron Artery Dis. 2006 May;17(3):261-9. — View Citation

Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE Jr, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, Williams DO; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009 Dec 1;120(22):2271-306. doi: 10.1161/CIRCULATIONAHA.109.192663. Epub 2009 Nov 18. Erratum in: Circulation. 2010 Mar 30;121(12):e257. Dosage error in article text. — View Citation

Meneveau N, Séronde MF, Descotes-Genon V, Dutheil J, Chopard R, Ecarnot F, Briand F, Bernard Y, Schiele F, Bassand JP. Immediate versus delayed angioplasty in infarct-related arteries with TIMI III flow and ST segment recovery: a matched comparison in acute myocardial infarction patients. Clin Res Cardiol. 2009 Apr;98(4):257-64. doi: 10.1007/s00392-009-0756-z. Epub 2009 Feb 9. — View Citation

Nijveldt R, Beek AM, Hirsch A, Stoel MG, Hofman MB, Umans VA, Algra PR, Twisk JW, van Rossum AC. Functional recovery after acute myocardial infarction: comparison between angiography, electrocardiography, and cardiovascular magnetic resonance measures of microvascular injury. J Am Coll Cardiol. 2008 Jul 15;52(3):181-9. doi: 10.1016/j.jacc.2008.04.006. — View Citation

Sardella G, Mancone M, Bucciarelli-Ducci C, Agati L, Scardala R, Carbone I, Francone M, Di Roma A, Benedetti G, Conti G, Fedele F. Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial. J Am Coll Cardiol. 2009 Jan 27;53(4):309-15. doi: 10.1016/j.jacc.2008.10.017. — View Citation

Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT, Michalis LK, Serruys PW. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol. 2007 Aug 14;50(7):573-83. Epub 2007 Jul 30. — View Citation

Svilaas T, Vlaar PJ, van der Horst IC, Diercks GF, de Smet BJ, van den Heuvel AF, Anthonio RL, Jessurun GA, Tan ES, Suurmeijer AJ, Zijlstra F. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med. 2008 Feb 7;358(6):557-67. doi: 10.1056/NEJMoa0706416. — View Citation

Thiele H, Schindler K, Friedenberger J, Eitel I, Fürnau G, Grebe E, Erbs S, Linke A, Möbius-Winkler S, Kivelitz D, Schuler G. Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial. Circulation. 2008 Jul 1;118(1):49-57. doi: 10.1161/CIRCULATIONAHA.107.747642. Epub 2008 Jun 16. — View Citation

Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M; ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008 Dec;29(23):2909-45. doi: 10.1093/eurheartj/ehn416. Epub 2008 Nov 12. — View Citation

Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, Blumenthal RS, Lima JA. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998 Mar 3;97(8):765-72. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is the extent of MVO as assessed by CMRI, expressed as the ratio of MVO/left ventricular mass, in the MIMI and conventional groups.	The primary end-point will be reviewed by an independent CMRI core laboratory blinded to the group and the procedure.; MVO is defined as a hypoenhanced subendocardial area in the infarction core 2 or 10 minutes after contrast injection (dark zone). The total myocardial infarction is defined as the sum of hypoenhanced (dark zone) and hyperenhanced (white zone) signals 10 minutes after contrast injection. The CMRI procedure will be standardised with a specific documentation.	day of performing CMRI (between the fourth and the seventh day after randomization)
Secondary	Comparison of the MIMI approach and the conventional strategy on TIMI flow, myocardial blush, and ST-segment evolution before and after the first procedure.	Measurements: TIMI flow grade and TIMI frame count (a more sophisticated method for measuring the flow) at the end of the procedure; blush (a more precise evaluation than TIMI flow on angiography); and ST-segment evolution on the electrocardiogram (ECG) before and 60-90 minutes after the first procedure (core laboratory).	before and 60-90 minutes after the first procedure
Secondary	To measure TIMI flow and myocardial blush at the beginning and at end of the second procedure in the MIMI group, and to compare with those obtained at the end of the first procedure.	Measurements: TIMI flow grade, TIMI frame count, and blush at the beginning and at the end of the second procedure.	at the beginning and one minute after the end of the second procedure
Secondary	Thrombus burden assessment, and culprit artery diameter between each procedure in the MIMI group	Measurements: Thrombus volume and artery diameter at the thrombus location during the first and second procedure, and diameter of the implanted stent (done at the core laboratory).	during each procedure (0-48 hours)
Secondary	Assessment of the ST-segment after the second procedure in the MIMI group	Measurements: Maximal ST-segment elevation before and 60-90 minutes after the second procedure (done at the core laboratory).	at the beginning (puncture) and 60-90 min after the end of the second procedure
Secondary	Assessment of the impact of the MIMI procedure on hospital clinical events, infarction size (on CMRI) and complications due to the second procedure.	The following hospital critical events and complications that occur after the first procedure will be analyzed: cardiogenic shock, acute pulmonary oedema, recurrent myocardial infarction, culprit artery re-occlusion, stroke, major bleeding [Bovill et al. 1991], evaluation of no flow, coronary dissection, recurrent myocardial infarction, chest pain, decelerating angio flow, recurrent ST elevation, troponin elevation, severe renal insufficiency, access site bleeding, and access artery occlusion.; Measurement: CMRI infarction size.	from randomisation to an expected average 4 days stay before hospital discharge
Secondary	Assessment of the clinical impact of the MIMI procedure at 6 months	Measurements: In both groups, follow-up will be undertaken at 6 months by a phone call to the general practitioner, cardiologist or patient, to report the occurrence of: death, recurrent myocardial infarction, hospitalization(s) for cardiac insufficiency, and unscheduled revascularisation.	6 months after randomization
Secondary	Assessment of the microcirculatory resistance in patients in whom a pressure endocoronary wire was used.	Measurement: Index of microcirculatory resistance (IMR) just after stenting (first procedure for the conventional group and second procedure for the MIMI group)	after each procedure (0-48 hours)
Secondary	Hospitalization duration for both procedures	Measurements: Number of days in ICU	expected average time from randomisation to Intensive Care Unit (ICU) discharge of 4 days