REperfusion Facilitated by LOcal Adjunctive Therapy in ST-elevation Myocardial Infarction

NCT ID: NCT01747174

Last Updated: 2015-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 247 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2014-12-31

Brief Summary

The purpose of this study is to determine whether intra-coronary adenosine or sodium nitroprusside (SNP) delivered selectively via a thrombus aspiration catheter (or if unsuccessful via a coronary microcatheter) following thrombus aspiration in Primary Percutaneous Coronary Intervention (P-PCI) reduces microvascular obstruction (MVO) parameters and infarct size as measured with cardiac MRI, compared with standard treatment following thrombus aspiration in patients presenting with ST-elevation myocardial infarction (STEMI).

Detailed Description

>100,000 patients suffering STEMI present in the UK each year. P-PCI in the UK is increasing exponentially. In 2004 there were <1500 P-PCI and in 2007 and 2008 these figures had increased to 5902 and 9224 respectively (BCIS database).

Although P-PCI delivered quickly is more effective than thrombolysis, the efficacy of this, essentially mechanical, technique is limited by the unpredictable phenomenon of no-reflow and the under-stated lesser degrees of MVO. As more UK centres adopt P-PCI the dilemma of how to attenuate MVO will remain. Currently there is no consensus on the optimal management to prevent or attenuate MVO particularly when thrombus laden lesions are treated with P-PCI.

There is divergent clinical practice, even within institutions, in the UK and worldwide. This is because there is no solid evidence base to inform clinicians. The current options for interventional cardiologists are:

1. Routinely aspirate thrombus and give IC vasodilator during the intervention but only in high burden thrombus formation lesions.

2. Perform a standard P-PCI only and then give IV vasodilator if angiographic no-reflow develops.

3. Routinely consider that angiographically silent MVO (i.e a grade below true "no-reflow") may have important impact on infarct size and clinical outcome and treat prophylactically.

Few if any clinicians follow this thinking. Indeed, it appears impossible to predict the incidence of (no-reflow/MVO) from the presenting angiogram (pre- or post- wire or balloon) and it can be argued that irrespective of thrombus burden it would be better to undertake prophylactic treatment in all patients, following the use of aspiration catheter, with delivery of agents able, in theory at least, to reduce (angiographically undetectable) MVO. Several studies of IC adenosine or SNP have shown favourable effects in attenuating MVO. However, the size of effect with either drug and whether indeed there is a difference between them in reducing MVO and infarct size is undetermined.

The objectives of our proposed study are to determine:

1. Whether adjunctive pharmaco-therapy at time of P-PCI and following thrombus aspiration, reduces CMR-determined MVO and infarct size.

2. Whether there is a difference between adenosine and SNP in reducing CMR-detected MVO and infarct size, both given selectively and distally via a thrombus aspiration catheter or a coronary microcatheter.

3. The correlation of angiographic, including the recently designed computer-assisted myocardial blush quantification 'Quantitative Blush Evaluator'(QuBE), and other myocardial perfusion markers, with CMR detected MVO and infarct size, as well as with clinical outcome (MACE) at 30 days.

Conditions

ST-elevation Myocardial Infarction (STEMI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Std PCI + Intra-coronary (IC) Adenosine

IC Adenosine in to IRA (following thrombus aspiration) with further dose via guide catheter following coronary stent deployment.

Group Type: EXPERIMENTAL

IC Adenosine

Intervention Type: DRUG

IC Adenosine 1mg injected distally via micro-catheter in to IRA following thrombus aspiration with further dose (1mg if IRA is RCA otherwise 2mg) via guide catheter following coronary stent deployment.

Standard PCI

Intervention Type: PROCEDURE

PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.

Std PCI + IC Sodium Nitroprusside (SNP)

IC SNP in to IRA (following thrombus aspiration) with further dose via guide catheter following coronary stent deployment.

Group Type: EXPERIMENTAL

IC Sodium nitroprusside (SNP)

Intervention Type: DRUG

IC SNP 250mcg injected distally via micro-catheter distally in to IRA following thrombus aspiration with further 250 mcg dose delivered via guide catheter following coronary stent deployment.

Standard PCI

Intervention Type: PROCEDURE

PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.

Std PCI

Standard PCI only

Group Type: ACTIVE_COMPARATOR

Standard PCI

Intervention Type: PROCEDURE

PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.

Interventions

IC Adenosine

IC Adenosine 1mg injected distally via micro-catheter in to IRA following thrombus aspiration with further dose (1mg if IRA is RCA otherwise 2mg) via guide catheter following coronary stent deployment.

Intervention Type: DRUG

IC Sodium nitroprusside (SNP)

IC SNP 250mcg injected distally via micro-catheter distally in to IRA following thrombus aspiration with further 250 mcg dose delivered via guide catheter following coronary stent deployment.

Intervention Type: DRUG

Standard PCI

PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.

Intervention Type: PROCEDURE

Other Intervention Names

Adenocor; Sodium pentacyanonitrosylferrate(II); Sodium nitroferricyanide; Sodium pentacyanonitrosylferrate; SNP

Eligibility Criteria

Inclusion Criteria

• ≥ 18 years age.
• Informed ASSENT (verbal consent) prior to angiography.
• STEMI ≤ 6 hrs of symptom onset, requiring primary reperfusion by PCI.
• Single-vessel coronary artery disease (non culprit disease ≤70% stenosis at angiography)
• TIMI flow 0/I at angiography.

Exclusion Criteria

• Contraindications to: P-PCI *, CMR**, contrast agents, or study medications: Adenosine***, SNP****, Aspirin, Thienopyridine and Bivalirudin.
• SBP ≤ 90mmHg
• Cardiogenic Shock
• Previous Q wave myocardial infarction
• Culprit lesion not identified or located in a by-pass graft
• Stent thrombosis.
• Left main disease.
• Known severe asthma.
• Known stage 4 or 5 chronic kidney disease (eGFR<30ml/min).
• Pregnancy.

Notes:

• ** Absolute contra-indication to CMR (Pacemaker, ICD, intra-cranial metal clips).
• *** Contraindications to Adenosine (known hypersensitivity to Adenosine, sick sinus syndrome, second or third degree atrio-ventricular block - except in patients with functioning artificial pacemaker, long QT syndrome has been defined as QTc > 450 ms at baseline). ECG will be undertaken just after the first dose of the study drug and QT/QTc will be recorded and compared to the baseline. If the QTc recorded after the first dose of the study drug exceeds 450ms or there is an increase in the QT/QTc of > 60 ms from baseline, the second dose will be abandoned and this will be recorded.
• **** Contraindications to SNP (known hypersensitivity to SNP, compensatory hypertension - as may be seen in arteriovenous shunts or coarctation of the aorta, high output failure, congenital optic atrophy or tobacco amblyopia).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospitals, Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony H Gershlick, MBBS, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

Glenfield Hospital

Leicester, Leicestershire, United Kingdom

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, United Kingdom

University Hospital

Coventry, West Midlands, United Kingdom

Leeds General Infirmary

Leeds, West Yorkshire, United Kingdom

Countries

United Kingdom

References

Nazir SA, McCann GP, Greenwood JP, Kunadian V, Khan JN, Mahmoud IZ, Blackman DJ, Been M, Abrams KR, Shipley L, Wilcox R, Adgey AA, Gershlick AH. Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial. Eur Heart J. 2016 Jun 21;37(24):1910-9. doi: 10.1093/eurheartj/ehw136. Epub 2016 May 4.

Reference Type: DERIVED

PMID: 27147610 (View on PubMed)

Nazir SA, Khan JN, Mahmoud IZ, Greenwood JP, Blackman DJ, Kunadian V, Been M, Abrams KR, Wilcox R, Adgey AA, McCann GP, Gershlick AH. The REFLO-STEMI trial comparing intracoronary adenosine, sodium nitroprusside and standard therapy for the attenuation of infarct size and microvascular obstruction during primary percutaneous coronary intervention: study protocol for a randomised controlled trial. Trials. 2014 Sep 25;15:371. doi: 10.1186/1745-6215-15-371.

Reference Type: DERIVED

PMID: 25252600 (View on PubMed)

Other Identifiers

2010-023211-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

09/150/28

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CLRN 53469

Identifier Type: -

Identifier Source: org_study_id