Study Evaluating the Use of Vasodilators to Reduce Infarct Size and Microvascular Obstruction in ST-elevation MI (MVO)

This study is currently recruiting participants.
Verified March 2014 by University Hospitals, Leicester
Sponsor:
Information provided by (Responsible Party):
University Hospitals, Leicester
ClinicalTrials.gov Identifier:
NCT01747174
First received: November 20, 2012
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
ST-elevation Myocardial Infarction (STEMI)
Drug: IC Adenosine
Drug: IC Sodium nitroprusside (SNP)
Procedure: Standard PCI
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University Hospitals, Leicester:

Primary Outcome Measures:
  • CMR measured infarct size (% LV mass) [ Time Frame: 48-72 hours post procedure ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • CMR incidence and extent of MVO (% LV mass) [ Time Frame: 48-72 hours post procedure ] [ Designated as safety issue: Yes ]
  • CMR measured myocardial salvage index, haemorrhage, LV EF and volumes [ Time Frame: 48-72 hours post procedure ] [ Designated as safety issue: Yes ]
  • Myocardial Blush Grade assessed by validated computer software 'Quantitative Blush Evaluator' (QuBE [ Time Frame: During P-PCI ] [ Designated as safety issue: No ]
  • Incidence pre- and post- procedure angiographic true "no-reflow" [ Time Frame: During P-PCI ] [ Designated as safety issue: No ]
  • Any in-patient clinical events [ Time Frame: Within 6 months from presentation with, and PCI for, STEMI ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
  • Echocardiographic assessment of LV [ Time Frame: 6-8 weeks post-procedure/MI ] [ Designated as safety issue: No ]
    To include end systolic/diastolic volumes, EF +/- wall motion index

  • Corrected TIMI Frame Count [ Time Frame: During procedure ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 240
Study Start Date: October 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Procedure: Standard PCI
PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.
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.
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.
Active Comparator: Std PCI
Standard PCI only
Procedure: Standard PCI
PCI procedure with thrombectomy (via aspiration catheter) and bivalirudin given as standard.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01747174

Contacts
Contact: Anthony H Gershlick, MBBS FRCP +44 (0) 116 258 3035 agershlick@aol.com
Contact: Sheraz A Nazir, MBBChir MRCP +44 (0) 116 258 3244 sn191@le.ac.uk

Locations
United Kingdom
Glenfield Hospital Recruiting
Leicester, Leicestershire, United Kingdom, LE3 9QP
Contact: Sheraz A Nazir, MBBChir MRCP    +44 (0) 116 258 3244    sn191@le.ac.uk   
Principal Investigator: Anthony H Gershlick, MBBS FRCP         
Freeman Hospital Recruiting
Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
Contact: Vijay Kunadian, MBBS MD FRCP    +44 (0) 191 222 5797    vijay.kunadian@ncl.ac.uk   
Principal Investigator: Vijay Kunadian, MBBS MD FRCP         
University Hospital Recruiting
Coventry, West Midlands, United Kingdom, CV2 2DX
Contact: Martin Been, MD, FRCP    +44 (0) 24 7696 5672    martin.been@uhcw.nhs.uk   
Principal Investigator: Martin Been, MBChB, MD, FRCP         
Leeds General Infirmary Recruiting
Leeds, West Yorkshire, United Kingdom, LS1 3EX
Contact: John Greenwood, MBChB PhD    +44 (0) 113 2432799    J.Greenwood@leeds.ac.uk   
Principal Investigator: John Greenwood, MBChB PhD         
Royal Derby Hospital Recruiting
Derby, United Kingdom, DE22 3NE
Contact: Kamal Chitkara, MD, MRCP    +44 (0) 1332 340131    kamal.chitkara@nhs.net   
Principal Investigator: Kamal Chitkara, MD, MRCP         
Sponsors and Collaborators
University Hospitals, Leicester
Investigators
Principal Investigator: Anthony H Gershlick, MBBS, FRCP University of Leicester
  More Information

No publications provided

Responsible Party: University Hospitals, Leicester
ClinicalTrials.gov Identifier: NCT01747174     History of Changes
Other Study ID Numbers: CLRN 53469, 2010-023211-34, 09/150/28
Study First Received: November 20, 2012
Last Updated: March 10, 2014
Health Authority: United Kingdom: National Institute for Health Research

Keywords provided by University Hospitals, Leicester:
STEMI
Microvascular Obstruction
No-reflow
Adenosine
Sodium Nitroprusside

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Adenosine
Nitroprusside
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on April 23, 2014