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ST-elevation Myocardial Infarction (STEMI)Phase 2REFLO-STEMINCT01747174

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

A Phase 2 study testing IC Adenosine, IC Sodium nitroprusside (SNP) and Standard PCI in people with ST-elevation Myocardial Infarction (STEMI), run by University Hospitals, Leicester at 4 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IC Adenosine, IC Sodium nitroprusside (SNP) and Standard PCI
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
247 participants
Where
4 sitesUnited Kingdom
Study dates
Oct 2011to Dec 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 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.

Who cannot join

  • 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.
Show all 15Show fewer
  • 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).

Trial locations and contacts

4 sites in 1 country.

United Kingdom4 sites

  • University Hospital

    Coventry, West Midlands, CV2 2DX

  • Leeds General Infirmary

    Leeds, West Yorkshire, LS1 3EX

  • Glenfield Hospital

    Leicester, Leicestershire, LE3 9QP

  • Freeman Hospital

    Newcastle upon Tyne, Tyne and Wear, NE7 7DN

Other trials in United Kingdom

About this study

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

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).

Read the 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.
Being tested
IC Adenosine, IC Sodium nitroprusside (SNP), Standard PCI
Keywords
STEMI, Microvascular Obstruction, No-reflow, Adenosine, Sodium Nitroprusside
Medical subject headings
ST Elevation Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IC AdenosineDrug

    Also called Adenocor

    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.

  • IC Sodium nitroprusside (SNP)Drug

    Also called Sodium pentacyanonitrosylferrate(II), Sodium nitroferricyanide, Sodium pentacyanonitrosylferrate, 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.

  • Standard PCIProcedure or surgery

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

Study groups in NCT01747174
Study groupRoleWhat they receive
Std PCI + Intra-coronary (IC) AdenosineExperimentalIC Adenosine in to IRA (following thrombus aspiration) with further dose via guide catheter following coronary stent deployment.
Receives: Drug: IC Adenosine; Procedure: Standard PCI
Std PCI + IC Sodium Nitroprusside (SNP)ExperimentalIC SNP in to IRA (following thrombus aspiration) with further dose via guide catheter following coronary stent deployment.
Receives: Drug: IC Sodium nitroprusside (SNP); Procedure: Standard PCI
Std PCIActive comparatorStandard PCI only
Receives: Procedure: Standard PCI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CMR measured infarct size (% LV mass)

    Measured: 48-72 hours post procedure

Secondary outcomes (9)

  1. CMR incidence and extent of MVO (% LV mass)

    Measured: 48-72 hours post procedure

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

    Measured: 48-72 hours post procedure

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

    Measured: During P-PCI

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

    Measured: During P-PCI

  5. Any in-patient clinical events

    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).

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

  6. Overall MACE

    MACE: composite of death, need for target lesion revascularization, recurrent MI, severe heart failure, and CVA.

    Measured: 1 month

  7. Degree of ST segment resolution on ECG

    Measured: Assessed immediately following P-PCI (expected on average 1 hour)

  8. Echocardiographic assessment of LV

    To include end systolic/diastolic volumes, EF +/- wall motion index

    Measured: 6-8 weeks post-procedure/MI

  9. Corrected TIMI Frame Count

    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.

    Measured: During procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2012 (estimated)
  2. Study startOct 2011
  3. Primary completionOct 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
247 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01747174
Sponsor's protocol ID
CLRN 53469
Other IDs
2010-023211-34, 09/150/28
Acronym
REFLO-STEMI
Status last verified
Jun 2015
First submitted
20 Nov 2012
Last updated
16 Jun 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27147610

  • 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.

    PubMed 25252600

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IC Adenosine, IC Sodium nitroprusside (SNP) and Standard PCI in people with ST-elevation Myocardial Infarction (STEMI), run by University Hospitals, Leicester at 4 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CMR measured infarct size (% LV mass) (time frame: 48-72 hours post procedure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01747174, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2015.

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