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

Information source: University Hospitals, Leicester
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: ST-elevation Myocardial Infarction (STEMI)

Intervention: IC Adenosine (Drug); IC Sodium nitroprusside (SNP) (Drug); Standard PCI (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: University Hospitals, Leicester

Official(s) and/or principal investigator(s):
Anthony H Gershlick, MBBS, FRCP, Principal Investigator, Affiliation: University of Leicester

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).

Clinical Details

Official title: Randomized Controlled Trial Comparing Intracoronary Administration of Adenosine or Sodium Nitroprusside to Control for Attenuation of Microvascular Obstruction During Primary Percutaneous Coronary Intervention

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: CMR measured infarct size (% LV mass)

Secondary outcome:

CMR incidence and extent of MVO (% LV mass)

CMR measured myocardial salvage index, haemorrhage, LV EF and volumes

Myocardial Blush Grade assessed by validated computer software 'Quantitative Blush Evaluator' (QuBE

Incidence pre- and post- procedure angiographic true "no-reflow"

Any in-patient clinical events

Overall MACE

Degree of ST segment resolution on ECG

Echocardiographic assessment of LV

Corrected TIMI Frame Count

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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:

- * Exclusion criteria for P-PCI (presentation timing, inadequate arterial access etc);

patient unable to tolerate "prolonged" PCI procedure (in operators' opinion).

- ** 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).

Locations and Contacts

Glenfield Hospital, Leicester, Leicestershire LE3 9QP, United Kingdom

Freeman Hospital, Newcastle upon Tyne, Tyne and Wear NE7 7DN, United Kingdom

University Hospital, Coventry, West Midlands CV2 2DX, United Kingdom

Leeds General Infirmary, Leeds, West Yorkshire LS1 3EX, United Kingdom

Additional Information

Starting date: October 2011
Last updated: June 15, 2015

Page last updated: August 23, 2015

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