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

NCT01747174 | Completed Phase 2 DMC

• 3 other identifiers: CLRN 534692010-023211-3409/150/28
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 4

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).

Conditions

ST-elevation Myocardial Infarction (STEMI)

Keywords

STEMI; Microvascular Obstruction; No-reflow; Adenosine; Sodium Nitroprusside

Outcome Measures

Primary Outcomes (1)

• CMR measured infarct size (% LV mass)

  48-72 hours post procedure

Secondary Outcomes (9)

• CMR incidence and extent of MVO (% LV mass)

  48-72 hours post procedure

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

  48-72 hours post procedure

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

  During P-PCI

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

  During P-PCI

• Any in-patient clinical events

  Within 6 months from presentation with, and PCI for, STEMI

Study Arms (3)

Std PCI + Intra-coronary (IC) Adenosine

EXPERIMENTAL

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

Drug: IC Adenosine; Procedure: Standard PCI

Std PCI + IC Sodium Nitroprusside (SNP)

EXPERIMENTAL

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

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

Std PCI

ACTIVE COMPARATOR

Standard PCI only

Procedure: Standard PCI

Interventions

IC Adenosine 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.

Also known as: Adenocor

Std PCI + Intra-coronary (IC) Adenosine

IC Sodium nitroprusside (SNP) 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.

Also known as: Sodium pentacyanonitrosylferrate(II), Sodium nitroferricyanide, Sodium pentacyanonitrosylferrate, SNP

Std PCI + IC Sodium Nitroprusside (SNP)

Standard PCI PROCEDURE

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

Std PCI; Std PCI + IC Sodium Nitroprusside (SNP); Std PCI + Intra-coronary (IC) Adenosine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospitals, Leicester: lead

Study Sites (4)

Glenfield Hospital

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Freeman Hospital

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

Location

University Hospital

Coventry, West Midlands, CV2 2DX, United Kingdom

Location

Leeds General Infirmary

Leeds, West Yorkshire, LS1 3EX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 27147610 DERIVED

• 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.

  PMID: 25252600 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Nitroprusside

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Officials

• Anthony H Gershlick, MBBS, FRCP

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: December 11, 2012
• Study Start: October 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 16, 2015

Record last verified: 2015-06

Locations

GB (4)