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NCT Number: NCT06128993

Trans-coronary Cooling and Dilution for Cardioprotection During Revascularisation for ST-elevation Myocardial Infarction

A heart attack (myocardial infarction) occurs when an artery supplying blood to the heart is suddenly blocked resulting in damage to the heart muscle.

Patients presenting to hospital with a heart attack undergo an immediate angiogram (x-ray of the arteries in the heart) and are usually treated immediately with a balloon and stent to open their blocked artery. This procedure is called "primary percutaneous coronary intervention" (or primary PCI for short).

An angiogram is a routine procedure that involves insertion of fine plastic tube (catheter) into either the groin or wrist under local anaesthetic. The tube is passed into the artery in the heart and X-ray pictures are taken to find out if the arteries are blocked. Blocked arteries can usually be opened by passing a small balloon into the artery, via the fine plastic tube followed by placement of a stent (a fine metal coil) into the artery to prevent it from blocking again.

Although this treatment is very successful, it can result in damage to the heart muscle when the artery is opened. Cooling the entire body has been shown to reduce heart muscle damage during heart attacks in some patients but not in others; however, it is uncomfortable due to the shivering, expensive and can result in delays in opening the blocked artery.

The investigators are conducting a series of research studies to find out if cooling the heart muscle directly through the catheter being used for the normal primary angioplasty treatment using room temperature may be effective in preserving heart muscle, without the shortcomings of entire body cooling.

The investigators have already published an initial series of ten cases in which this treatment appeared to be feasible without causing significant clinical problems.

The present study is a pilot study designed to assess the rate of patient recruitment and feasibility of this new treatment while exploring some detailed outcomes measuring the restoration of blood flow within the coronary artery at the end of the procedure.

Ultimately if the present pilot study is successful, the investigators plan to go on to undertake a much larger randomised outcome study to determine definitively whether this treatment can help reduce heart attack size.

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Key information

Conditions

Myocardial Infarction Cardiomyopathies Cardiovascular Diseases Heart Diseases Infarction Ischemia Myocardial Ischemia Myocardial Reperfusion Injury Necrosis Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Reperfusion Injury Reperfusion Injury, Myocardial Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Harefield Hospital

Uxbridge, UB9 6JH, United Kingdom

Location status: Recruiting

About this study

The study population will comprise 60 patients with ST-Elevation Myocardial Infarction (STEMI) presenting to Harefield Hospital undergoing primary percutaneous coronary intervention (PCI).

The primary aim of this pilot trial is to investigate the recruitment rate feasibility and safety of undertaking a randomised trial of simple intracoronary coronary cooling and dilution through the guiding catheter during primary PCI for STEMI to reduce myocardial infarction size.

The secondary aims are as follows:

  • The study will explore the invasive haemodynamic assessment of coronary flow and microvascular function
  • The study will explore blood biomarkers before and after treatment for myocardial infarction
  • The study will explore myocardial salvage after treatment for myocardial infarction with magnetic resonance imaging (MRI) and subsequent final infarct size.

Patients will be randomised 1:1 in the catheterisation lab when coronary angiography has demonstrated a target lesion with proposed primary PCI. Patients randomised to the intervention will receive transcatheter cooling and dilution in addition to usual clinical care. Patients randomised to control will receive usual care alone.

A combined thermistor and pressure wire Coroventis™ (Abbott Vascular) with comparable tip stiffness to standard guidewires and in routine clinical use, will be used to perform the primary PCI procedure and to measure intracoronary temperature and pressure continually throughout all procedures in all patients. This will therefore limit the procedure to a simple single wire throughout strategy in most cases. In the event that the wire fails to function properly during or after the PCI procedure it may be changed for a new wire using standard interventional techniques as appropriate

Patients randomised to intracoronary cooling and dilution(n=30), will receive an intracoronary infusion of room temperature 0.9% Normal Saline solution through the guiding catheter which will commence immediately prior to crossing the coronary occlusion with the guidewire. Using a 3-way tap in the procedural manifold an infusion pressure of 150mmHg above systolic blood pressure achieved with a pressure bag will be used to achieve a target intracoronary temperature of 6-8 C° below the baseline temperature. The infusion will continue until 10 minutes after the lesion is crossed and distal flow is restored, with only brief interruptions as required for the clinical procedure. A maximum volume of 750ml will be infused. The primary angioplasty procedure itself will be undertaken according to standard local practice. Patients randomised to the control group (n=30) will undergo primary PCI according to standard local practice.

A complete physiological study including Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR), resistive reserve ratio (RRR) and index of microvascular resistance (IMR) to assess microcirculation will be measured 10 minutes after reperfusion in all patients.

Patients will go on to have blood taken on the next day for the analysis of a panel of biomarkers and comparison with pre-procedure levels and in addition to have a cardiac MRI scan prior to discharge and at 6 months.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Clinical ST-elevation myocardial infarction or equivalent (e.g. new onset LBBB)
  • <12 Hrs after symptom onset
  • Thrombolysis in myocardial infarction (TIMI) 0-1 coronary flow in a target vessel

Exclusion criteria

  • History of severe asthma
  • Pregnancy
  • Severe concomitant disease or conditions with a life expectancy of less than one year.

Treatment and study plan

Transcoronary cooling and dilution

Other

Transcoronary cooling and dilution

Standard of care

Other

Routine clinical care

Primary outcomes

  1. Recruitment rate

    Time frame: 1 year

    Patients recruited per month

  2. Feasibility (Number of studies where all the planned measurements have been collected / total studies)

    Time frame: 1 year

    Number of studies where all the planned measurements have been collected / total studies

  3. Safety (Adverse events should not be significantly higher in the treatment arm compared to control, nor plausibly caused by the treatment)

    Time frame: 1 year

    Adverse events should not be significantly higher in the treatment arm compared to control, nor plausibly caused by the treatment as assessed by CTCAE v5.0

Secondary outcomes

  1. Index of microvascular resistance (IMR) 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Distal coronary pressure during hyperaemia x mean transit time (mmHg·s)

  2. Fractional flow reserve (FFR) 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Distal coronary pressure/aortic pressure during hyperaemia

  3. Coronary flow reserve (CFR) 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Thermodilution-based ratio of hyperaemic coronary flow/basal flow

  4. Resistive reserve ratio (RRR) 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Index of microvascular resistance rest/hyperaemia

  5. Resting full-cycle ratio (RFR) 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    lowest value of distal coronary pressure/aortic pressure over the entire cardiac cycle at rest

  6. Intracoronary temperature change

    Time frame: 1 hour

    Intracoronary temperature change during cooling and dilution (°C)

  7. Infusion volume

    Time frame: 1 hour

    Total volume of intracoronary saline infused (ml)

  8. Infusion rate

    Time frame: 1 hour

    Total volume of intracoronary saline infused/infusion time (ml/min)

  9. Chest pain during study infusion

    Time frame: 1 hour

    Whether new chest pain arises, or chest pain increases during study infusion

  10. ECG changes during study infusion

    Time frame: 1 hour

    Amelioration or worsening of the ECG anomalies during study infusion (ST elevation/depression, T wave inversion, QT prolongation)

  11. Heart rhythm changes during study infusion

    Time frame: 1 hour

    Appearance or resolution of heart rhythm disturbances during study infusion (sinus tachycardia, supraventricular tachycardia, atrial tachycardia/fibrillation/flutter, ventricular tachycardia/flutter, ventricular fibrillation, sinus bradycardia, grade I, II, or III heart block, asystole.

  12. Myocardial blush grade 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Angiographic myocardial perfusion measurement based on visual assessment of the myocardium after contrast injection. Grading: 0, no myocardial blush or contrast density; 1, minimal myocardial blush or contrast density; 2, moderate myocardial blush or contrast density but less than that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery; and 3, normal myocardial blush or contrast density, comparable with that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery

  13. Thrombolysis in Myocardial Infarction (TIMI) flow 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Visual angiographic assessment of coronary flow. Grade 0 = no perfusion; grade 1 = penetration without perfusion; 2 = partial perfusion; 3 = complete perfusion

  14. ST segment resolution 10 mins after completion of percutaneous coronary intervention and study infusion

    Time frame: 1 hour

    Null, partial, or complete resolution of the ST elevation

  15. Heart Rhythm disturbance from baseline to 12 hours

    Time frame: 12 hours

    Appearance or resolution of heart rhythm disturbances in the 12 hours after the procedure (sinus tachycardia, supraventricular tachycardia, atrial tachycardia/fibrillation/flutter, ventricular tachycardia/flutter, ventricular fibrillation, sinus bradycardia, grade I, II, or III heart block, asystole.

  16. Haemodynamic compromise from baseline to 12 hours

    Time frame: 12 hours

    Society for Cardiovascular Angiography and Interventions (SCAI) class B or above

  17. Left ventricular ejection fraction (LVEF) at 48 hours

    Time frame: 2 days

    Simpson biplane (diastolic-systolic)/diastolic left ventricular volume on echocardiography

  18. Left ventricular ejection fraction (LVEF) at 6 months

    Time frame: 6 months

    Simpson biplane (diastolic-systolic)/diastolic left ventricular volume on echocardiography

  19. Wall motion score index (WMSI) at 48 hours

    Time frame: 48 hours

    The wall motion score index (WMSI) is an echocardiographic parameter that numerically sums the average scores for all left ventricular segments into a single parameter and then dividing by the number of segments. 1 Normal motion; 2 = hypokinesia; 3 = akinesia; 4 = dyskinesia.

  20. Wall motion score index (WMSI) at 6 months

    Time frame: 6 months

    The wall motion score index (WMSI) is an echocardiographic parameter that numerically sums the average scores for all left ventricular segments into a single parameter and then dividing by the number of segments. 1 Normal motion; 2 = hypokinesia; 3 = akinesia; 4 = dyskinesia.

  21. Global longitudinal strain (GLS) at 48 hours

    Time frame: 48 hours

    Echocardiographic speckle-tracking imaging that measures the systolic shortening of left ventricular segments as percentage of their diastolic length

  22. Global longitudinal strain (GLS) at 6 months

    Time frame: 6 months

    Echocardiographic speckle-tracking imaging that measures the systolic shortening of left ventricular segments as percentage of their diastolic length

  23. Length of stay

    Time frame: 3-5 days

    Duration of hospital length of stay

  24. Peak high-sensitivity cardiac troponin T (hs-cTnT, ng/l)

    Time frame: 1-3 days

    Myocardial injury marker. Highest hs-cTnT measurement during hospital stay

  25. N-terminal pro-brain natriuretic peptide (NT-proBNP, ng/l)

    Time frame: 1-3 days

    Heart failure marker. Highest NT-proBNP measurement during hospital stay

  26. Interleukin-1b

    Time frame: 1 day

    Biomarker of inflammation during myocardial infarction

  27. Interleukin-1 receptor antagonist

    Time frame: 1 day

    Biomarker of inflammation during myocardial infarction

  28. Interleukin-6

    Time frame: 1 day

    Biomarker of inflammation during myocardial infarction

  29. Interleukin-10

    Time frame: 1 day

    Biomarker of inflammation during myocardial infarction

  30. First pass microvascular obstruction extent (FP MVO)

    Time frame: 1-3 days

    Measured in 3 SAX levels to provide an index of %LV FP MVO

  31. First pass microvascular obstruction extent (FP MVO) at 6 months

    Time frame: 6 months

    Measured in 3 SAX levels to provide an index of %LV FP MVO

  32. Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI, adjusted for area at-risk

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  33. Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI, adjusted for area at-risk, at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  34. Late MVO (presence / absence) on LGE

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  35. Late MVO (presence / absence) on LGE at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  36. Initial infarct size (LGE)

    Time frame: 1-3 days

    Mass of infarcted myocardium calculated with the full-width at half-maximum method

  37. Infarct size (LGE) at 6 months

    Time frame: 6 months

    Mass of infarcted myocardium calculated with the full-width at half-maximum method

  38. Initial MSI (area-at-risk minus initial infarct size/area-at-risk)

    Time frame: 1-3 days

    Percentage of the area at risk (calculated with the Otsu method) that was not infarcted on late gadolinium enhancement (LGE) images using infarct size from the pre-discharge (Acute MSI)

  39. MSI (area-at-risk minus initial infarct size/area-at-risk) at 6 months

    Time frame: 6 months

    Percentage of the area at risk (calculated with the Otsu method) that was not infarcted on late gadolinium enhancement (LGE) images using infarct size from the follow-up (Final MSI) magnetic resonance imaging

  40. Left ventricular end-diastolic volume index (LVEDVI)

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  41. Left ventricular end-diastolic volume index (LVEDVI) at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  42. Left ventricular end-systolic volume index (LVESVI)

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  43. Left ventricular end-systolic volume index (LVESVI) at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  44. Cardiac Magnetic Resonance-based Left ventricular ejection fraction (LVEF)

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  45. Cardiac Magnetic Resonance-based Left ventricular ejection fraction (LVEF) at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  46. Myocardial haemorrhage (presence/absence)

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  47. Myocardial haemorrhage (presence/absence) at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  48. Myocardial haemorrhage extent (% of LV)

    Time frame: 1-3 days

    Cardiac magnetic resonance-based assessment

  49. Myocardial haemorrhage extent (% of LV) at 6 months

    Time frame: 6 months

    Cardiac magnetic resonance-based assessment

  50. Composite of all-cause mortality and hospitalization for heart failure at 6 weeks

    Time frame: 6 weeks

    Composite of all-cause mortality and hospitalization for heart failure at 6 weeks

  51. Hospitalization for heart failure at 6 weeks

    Time frame: 6 weeks

    Hospitalization for heart failure at 6 weeks

  52. Cardiovascular mortality at 6 weeks

    Time frame: 6 weeks

    Cardiovascular mortality at 6 weeks

  53. All-cause mortality at 6 weeks

    Time frame: 6 weeks

    All-cause mortality at 6 weeks

  54. Hospitalization for heart failure at 6 months

    Time frame: 6 months

    Hospitalization for heart failure at 6 months

  55. Cardiovascular mortality at 6 months

    Time frame: 6 months

    Cardiovascular mortality at 6 months

  56. Composite of all-cause mortality and hospitalization for heart failure at 6 months

    Time frame: 6 months

    Composite of all-cause mortality and hospitalization for heart failure at 6 months

  57. All-cause mortality at 6 months

    Time frame: 6 months

    All-cause mortality at 6 months

  58. Composite of all-cause mortality and hospitalization for heart failure at 12 months

    Time frame: 12 months

    Composite of all-cause mortality and hospitalization for heart failure at 12 months

  59. Hospitalization for heart failure at 12 months

    Time frame: 12 months

    Hospitalization for heart failure at 12 months

  60. Cardiovascular mortality at 12 months

    Time frame: 12 months

    Cardiovascular mortality at 12 months

Study contacts

Contact information is provided by the study sponsor or research team.

Ira Jakupovic

CONTACT

[email protected]

+44207 3518109

Miles C Dalby, MD

CONTACT

[email protected]

+441895 823737

Sponsors and collaborators

Lead sponsor

Royal Brompton & Harefield NHS Foundation Trust

Other

Registry information

Acronym: STEMI-Cool

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
Nov 13, 2023
Registry last updated
Jan 31, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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