Randomized Study to Assess the Effect of ThRombus Aspiration on Flow Area in STEMI Patients

Coronary Artery Disease Clinical Trial

— TROFI  

Official title:

Randomized Study to Assess the Effect of ThRombus Aspiration on Flow Area in STEMI Patients: an Optical Frequency Domain Imaging (OFDI) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01271361
• Other study ID #: T114E4
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 5, 2011
• Last updated: December 6, 2012
• Start date: November 2010
• Est. completion date: December 2012

Study information

• Verified date: December 2012
• Source: Terumo Europe N.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Dutch Health Care InspectorateNetherlands: Medical Ethics Review Committee (METC)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeFrance: Conseil National de l'Ordre des MédecinsFrance: French Data Protection AuthorityGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesDenmark: Danish Medicines AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of the study it to evaluate whether primary percutaneous coronary intervention (primary PCI) with a new thrombectomy device as compared to primary PCI without thrombectomy increases minimal flow area after stenting for treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI) as assessed by OFDI.

Description:

Primary percutaneous coronary intervention has been well established as the treatment of choice for the majority of patients presenting with acute ST elevation myocardial infarction (STEMI). However primary PCI alone is unable to remove intracoronary thrombus and this often results in distal embolisation, no reflow which in turn leads to impaired myocardial perfusion. This can result in left ventricular dysfunction and subsequently increased mortality.

The use of thrombectomy devices during percutaneous coronary intervention in the setting of acute ST elevation myocardial infarction has been recently shown to improve epicardial, myocardial perfusion, angiographical TIMI flow, blush score, or result in less embolisation. Moreover thrombus aspiration or rheolysis has been shown to decrease cardiac death and repeat myocardial infarction.

It is estimated that late stent malapposition is more common after stenting in the course of primary PCI as compared with elective PCI, and may predispose to stent thrombosis. Late malapposition may be related to underdeployment of stents at the time of primary PCI, and this may be due in part to thrombus behind the stent, which subsequently resolves and leads to stent malapposition. Removal of thrombus before stenting potentially could lead to better stent expansion and less late malapposition.

On the other hand, the impact of thrombus on acute and chronic luminal dimension is still unclear in a setting of primary PCI. After stenting, such thrombus either I) protrude into the lumen through the mesh of metallic stent struts or II) is crushed between the vessel wall and stent. Theoretically, the protruded thrombus can hinder the intra-luminal flow immediately after stenting, while the resorption of crushed thrombus against vessel wall might result at long term in stent malaposition.

Due to the limited ability of the conventional angiography and the intravascular ultrasound (IVUS) to detect thrombus, these aspects have not been investigated.

Optical coherence tomography has recently been shown to be feasible and to provide valuable information in the setting of acute myocardial infarction. This imaging modality has been shown to be even more sensitive to detect intraluminal mass (i.e. thrombus) and offers unique possibilities of analysis of coronary intervention in acute myocardial infarction.

TERUMO OFDI is a novel optical imaging device that uses a scanning laser as light source which centre wavelength is around 1.3 μm with sweeping range over 100 nm. The echo-time delay and the amplitude of light reflected from the tissue microstructure at different depths are determined by processing the interference between the tissue sample and a fixed reference mirror.

Compared to the conventional OCT imaging devices, OFDI has a higher temporal frame rate (160 frames/sec), with a faster pullback speed of maximally up to 40 mm/s. The safety and performance of the device has been investigated in the First-in-man study enrolling 19 patients where both IVUS and OFDI were performed. In the study, OFDI was associated with no device-related adverse events, and with a good correlation with IVUS measurement.

We hypothesize that TERUMO Eliminate® thrombectomy device will reduce the thrombus burden in STEMI patients and this will result in less intraluminal material and larger flow area, measured with OFDI. This will be clinically translated in a better restoration of blood flow and reduce further damage of the myocardium.

In addition, a reduction of thrombus burden would eventually result in less stent malaposition at 6 months. Given the benefits of reducing thrombus burden in STEMI as described above, the study may have important implications on the prove of the effectiveness of the thrombectomy device and the use of this imaging modality to assess its efficacy. To best assess benefits of thrombus removal, a randomized controlled study was considered the most appropriate method.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: December 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient is at least 18 years of age.

• Patients with a ST-elevation Myocardial Infarction documented in an ambulance or in a Cathlab with =2 mm ST segment elevation in at least two contiguous leads, presenting in the Cathlab <12 hours after the onset of symptoms lasting =20 min and having an angiographical visible stenosis (>30%) or TIMI= II in de-novo, native, previously unstented vessel.

• The single vessel coronary artery disease.

• Signed Informed Consent.

• The patient understands and accepts clinical follow-up and OFDI controls.

• Patients residence is in the area covered by hospital. Angiographic

• Vessel size should match available Nobori stent sizes (<4.0 mm, and >2.0 mm by visual assessment).

Additional Inclusion criteria (applicable only for France)

• Patients residence is in the area covered by hospital.

• Patient is affiliated to social security or equivalent system.

Exclusion Criteria:

• Pregnancy and women of child bearing potential (less than 50 years of age).

• Known intolerance to aspirin, clopidogrel, heparin, stainless steel, Biolimus A9, contrast material.

• Diameter Stenosis <30% in the target lesion.

• The multi-vessel coronary artery disease (DS>50%).

• Unprotected left main disease with a diameter stenosis of >30% by visual assessment.

• Distal vessel occlusion.

• Severe tortuous, calcified or angulated coronary anatomy of the study vessel that in the opinion of the investigator would result in sub-optimal imaging or excessive risk of complication from placement of an OFDI catheter.

• Fibrinolysis prior to PCI.

• Known thrombocytopaenia (PLT< 100,000/mm3).

• Contraindication to PCI, stenting, ASA, clopidogrel.

• Active bleeding or coagulopathy or patients at chronic anticoagulation therapy.

• Cardiogenic Shock.

• Significant comorbidities precluding clinical follow-up (as judged by investigators).

• Major planned surgery that requires discontinuation of dual antiplatelet therapy.

• Proximal RCA stenosis (>30%) if the infarct-related artery is mid-RCA or distal-RCA.

• People under judicial protection.

• A patient who has congenital heart disease, severe cardiac valve disorder and/or myocardial disease (excluding status post MI).

• Patient participating in other clinical research study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Infarction
• Myocardial Ischemia
• STEMI

Intervention

Procedure:
• primary PCI with thrombectomy
thrombectomy is performed before implantation of a drug eluting stent
• primary PCI without thrombectomy
no thrombectomy is performed before the implantation of a drug eluting stent

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital Skejby	Aarhus
France	Clinique Pasteur	Toulouse
Germany	Universität Leipzig - Herzzentrum	Leipzig
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Maastad Hospital	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Terumo Europe N.V.

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Netherlands, 

References & Publications (23)

Burzotta F, Trani C, Romagnoli E, Mazzari MA, Rebuzzi AG, De Vita M, Garramone B, Giannico F, Niccoli G, Biondi-Zoccai GG, Schiavoni G, Mongiardo R, Crea F. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty (REMEDIA) trial. J Am Coll Cardiol. 2005 Jul 19;46(2):371-6. — View Citation

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De Luca G, Dudek D, Sardella G, Marino P, Chevalier B, Zijlstra F. Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials. Eur Heart J. 2008 Dec;29(24):3002-10. doi: 10.1093/eurheartj/ehn389. Epub 2008 Sep 5. Review. — View Citation

Gonzalo N, Barlis P, Serruys PW, Garcia-Garcia HM, Onuma Y, Ligthart J, Regar E. Incomplete stent apposition and delayed tissue coverage are more frequent in drug-eluting stents implanted during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction than in drug-eluting stents implanted for stable/unstable angina: insights from optical coherence tomography. JACC Cardiovasc Interv. 2009 May;2(5):445-52. doi: 10.1016/j.jcin.2009.01.012. — View Citation

Grayson AD, Moore RK, Jackson M, Rathore S, Sastry S, Gray TP, Schofield I, Chauhan A, Ordoubadi FF, Prendergast B, Stables RH; North West Quality Improvement Programme in Cardiac Interventions. Multivariate prediction of major adverse cardiac events after 9914 percutaneous coronary interventions in the north west of England. Heart. 2006 May;92(5):658-63. Epub 2005 Sep 13. — View Citation

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Haeck JD, Koch KT, Bilodeau L, Van der Schaaf RJ, Henriques JP, Vis MM, Baan J Jr, Van der Wal AC, Piek JJ, Tijssen JG, Krucoff MW, De Winter RJ. Randomized comparison of primary percutaneous coronary intervention with combined proximal embolic protection and thrombus aspiration versus primary percutaneous coronary intervention alone in ST-segment elevation myocardial infarction: the PREPARE (PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation) study. JACC Cardiovasc Interv. 2009 Oct;2(10):934-43. doi: 10.1016/j.jcin.2009.07.013. — View Citation

Hara H, Nakamura M, Komatsu H, Ikeda N, Shinji H, Makino K, Itaya H, Yamamoto M, Itou N, Tsunoda T, Sugi K. Comparison of the in vitro performance of 6 and 7 French aspiration catheters. EuroIntervention. 2007 Feb;2(4):487-92. — View Citation

Ikari Y, Sakurada M, Kozuma K, Kawano S, Katsuki T, Kimura K, Suzuki T, Yamashita T, Takizawa A, Misumi K, Hashimoto H, Isshiki T; VAMPIRE Investigators. Upfront thrombus aspiration in primary coronary intervention for patients with ST-segment elevation acute myocardial infarction: report of the VAMPIRE (VAcuuM asPIration thrombus REmoval) trial. JACC Cardiovasc Interv. 2008 Aug;1(4):424-31. doi: 10.1016/j.jcin.2008.06.004. — View Citation

Johansson P, Lundén M, Ekström L, Grip L, Wennerblom B. Intensive use of intravascular ultrasound during coronary angioplasty. A six-month campaign. Scand Cardiovasc J. 2001 Mar;35(2):75-9. — View Citation

Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol. 2007 Sep 4;50(10):933-9. Epub 2007 Aug 20. — 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

Sardella G, Mancone M, Nguyen BL, De Luca L, Di Roma A, Colantonio R, Petrolini A, Conti G, Fedele F. The effect of thrombectomy on myocardial blush in primary angioplasty: the Randomized Evaluation of Thrombus Aspiration by two thrombectomy devices in acute Myocardial Infarction (RETAMI) trial. Catheter Cardiovasc Interv. 2008 Jan 1;71(1):84-91. — 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

Sianos G, Papafaklis MI, Vaina S, Daemen J, van Mieghem CA, Van Domburg RT, Michalis LK, de Jaegere P, Serruys PW. Rheolytic thrombectomy in patients with ST-elevation myocardial infarction and large thrombus burden: the Thoraxcenter experience. J Invasive Cardiol. 2006 Jul;18 Suppl C:3C-7C. — View Citation

Silva-Orrego P, Colombo P, Bigi R, Gregori D, Delgado A, Salvade P, Oreglia J, Orrico P, de Biase A, Piccalò G, Bossi I, Klugmann S. Thrombus aspiration before primary angioplasty improves myocardial reperfusion in acute myocardial infarction: the DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) study. J Am Coll Cardiol. 2006 Oct 17;48(8):1552-9. Epub 2006 Sep 26. — View Citation

Svilaas T, van der Horst IC, Zijlstra F. Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS)--study design. Am Heart J. 2006 Mar;151(3):597.e1-597.e7. — 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

Vlaar PJ, Svilaas T, van der Horst IC, Diercks GF, Fokkema ML, de Smet BJ, van den Heuvel AF, Anthonio RL, Jessurun GA, Tan ES, Suurmeijer AJ, Zijlstra F. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet. 2008 Jun 7;371(9628):1915-20. doi: 10.1016/S0140-6736(08)60833-8. — View Citation

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Zijlstra F, Hoorntje JC, de Boer MJ, Reiffers S, Miedema K, Ottervanger JP, van 't Hof AW, Suryapranata H. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med. 1999 Nov 4;341(19):1413-9. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	minimal flow area assessed by OFDI	Flow area is defined as: (Stent area + incomplete stent apposition area) - (intraluminal defect area attached to the wall + intraluminal defect area free from the wall)	at baseline procedure (post-stenting)	No
Secondary	normalised minimal flow area	defined as the ratio of minimal flow divided by stent area at the site of the minimal flow area	at baseline procedure (post stenting)	No
Secondary	mean flow area/volume		at baseline procedure (post stenting) and at 6 months	No
Secondary	intraluminal defect area/volume		at baseline procedure (post stenting) and at 6 months	No
Secondary	mean stent area/volume		at baseline procedure (post stenting) and at 6 months	No
Secondary	percent of malapposed struts		at baseline procedure (post stenting) and at 6 months	No
Secondary	incomplete stent apposition (ISA) area/volume		at baseline procedure (post stenting) and at 6 months	No
Secondary	percent of struts with coverage		at 6 months	No
Secondary	healing index		at 6 months	No
Secondary	tissues prolapse area/volume		at 6 months	No
Secondary	procedure success	attainment of <30% residual stenosis of the target lesion and no in-hospital target vessel failure	at baseline procedure	No
Secondary	target vessel failure	defined as cardiac death, reinfarction in the territory of infarction related vessel (Q wave and non-Q wave), or clinically driven target vessel revascularization - and its individual components	at discharge, 1 month, 6 months and 12 months	Yes
Secondary	all-cause mortality		at discharge, 1 month, 6 months and 12 months	Yes
Secondary	cardiac death, non-cardiovascular death, vascular death		at discharge, 1 month, 6 months and 12 months	Yes
Secondary	any myocardial (re)infarction		at discharge, 1 month, 6 months and 12 months	Yes
Secondary	target vessel revascularization		at discharge, 1 month, 6 months and 12 months	Yes
Secondary	stent thrombosis according to ARC definition		at discharge, 1 month, 6 months and 12 months	Yes
Secondary	other serious adverse events (SAEs)		at discharge, 1 month, 6 months and 12 months	Yes