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REperfusion Facilitated by LOcal Adjunctive Therapy in ST-elevation Myocardial Infarction (REFLO-STEMI)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01747174
First Posted: December 11, 2012
Last Update Posted: June 16, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
University Hospitals, Leicester
November 20, 2012
December 11, 2012
June 16, 2015
October 2011
October 2014   (Final data collection date for primary outcome measure)
CMR measured infarct size (% LV mass) [ Time Frame: 48-72 hours post procedure ]
Same as current
Complete list of historical versions of study NCT01747174 on ClinicalTrials.gov Archive Site
  • CMR incidence and extent of MVO (% LV mass) [ Time Frame: 48-72 hours post procedure ]
  • CMR measured myocardial salvage index, haemorrhage, LV EF and volumes [ Time Frame: 48-72 hours post procedure ]
  • Myocardial Blush Grade assessed by validated computer software 'Quantitative Blush Evaluator' (QuBE [ Time Frame: During P-PCI ]
  • Incidence pre- and post- procedure angiographic true "no-reflow" [ Time Frame: During P-PCI ]
  • Any in-patient clinical events [ Time Frame: Within 6 months from presentation with, and PCI for, STEMI ]
    Includes: coronary artery re-occlusion, need for repeat PCI, recurrent chest pain with new ECG changes, incidence of clinical heart failure (symptoms plus basal crackles plus X-ray evidence of pulmonary congestion) and proven cerebrovascular accident (CVA).
  • Overall MACE [ Time Frame: 1 month ]
    MACE: composite of death, need for target lesion revascularization, recurrent MI, severe heart failure, and CVA.
  • Degree of ST segment resolution on ECG [ Time Frame: Assessed immediately following P-PCI (expected on average 1 hour) ]
  • Echocardiographic assessment of LV [ Time Frame: 6-8 weeks post-procedure/MI ]
    To include end systolic/diastolic volumes, EF +/- wall motion index
  • Corrected TIMI Frame Count [ Time Frame: During procedure ]
    TIMI frame count or TFC is defined as the number of cineframes required for contrast to reach a standardized distal coronary landmark in the culprit vessel.
  • CMR incidence and extent of MVO (% LV mass) [ Time Frame: 48-72 hours post procedure ]
  • CMR measured myocardial salvage index, haemorrhage, LV EF and volumes [ Time Frame: 48-72 hours post procedure ]
  • Myocardial Blush Grade assessed by validated computer software 'Quantitative Blush Evaluator' (QuBE [ Time Frame: During P-PCI ]
  • Incidence pre- and post- procedure angiographic true "no-reflow" [ Time Frame: During P-PCI ]
  • Any in-patient clinical events [ Time Frame: Within 6 months from presentation with, and PCI for, STEMI ]
    Includes: coronary artery re-occlusion, need for repeat PCI, recurrent chest pain with new ECG changes, incidence of clinical heart failure (symptoms plus basal crackles plus X-ray evidence of pulmonary congestion) and proven cerebrovascular accident (CVA).
  • Overall MACCE [ Time Frame: 6 months ]
    MACCE: composite of death, need for target lesion revascularization, recurrent MI, severe heart failure, and CVA.
  • Degree of ST segment resolution on ECG [ Time Frame: Assessed immediately following P-PCI (expected on average 1 hour) ]
  • Echocardiographic assessment of LV [ Time Frame: 6-8 weeks post-procedure/MI ]
    To include end systolic/diastolic volumes, EF +/- wall motion index
  • Corrected TIMI Frame Count [ Time Frame: During procedure ]
    TIMI frame count or TFC is defined as the number of cineframes required for contrast to reach a standardized distal coronary landmark in the culprit vessel.
Not Provided
Not Provided
 
REperfusion Facilitated by LOcal Adjunctive Therapy in ST-elevation Myocardial Infarction
Randomized Controlled Trial Comparing Intracoronary Administration of Adenosine or Sodium Nitroprusside to Control for Attenuation of Microvascular Obstruction During Primary Percutaneous Coronary Intervention
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).

>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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
ST-elevation Myocardial Infarction (STEMI)
  • Drug: 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.
    Other Name: Adenocor
  • 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.
    Other Names:
    • Sodium pentacyanonitrosylferrate(II)
    • Sodium nitroferricyanide
    • Sodium pentacyanonitrosylferrate
    • SNP
  • Procedure: Standard PCI
    PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.
  • Experimental: Std PCI + Intra-coronary (IC) Adenosine
    IC Adenosine in to IRA (following thrombus aspiration) with further dose via guide catheter following coronary stent deployment.
    Interventions:
    • Drug: IC Adenosine
    • Procedure: Standard PCI
  • Experimental: Std PCI + IC Sodium Nitroprusside (SNP)
    IC SNP in to IRA (following thrombus aspiration) with further dose via guide catheter following coronary stent deployment.
    Interventions:
    • Drug: IC Sodium nitroprusside (SNP)
    • Procedure: Standard PCI
  • Active Comparator: Std PCI
    Standard PCI only
    Intervention: Procedure: Standard PCI

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
247
December 2014
October 2014   (Final data collection date for primary outcome measure)

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).
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
 
NCT01747174
CLRN 53469
2010-023211-34 ( EudraCT Number )
09/150/28 ( Other Grant/Funding Number: NIHR EME )
Yes
Not Provided
Not Provided
University Hospitals, Leicester
University Hospitals, Leicester
Not Provided
Principal Investigator: Anthony H Gershlick, MBBS, FRCP University of Leicester
University Hospitals, Leicester
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP