Clinical trial NCT06128993: Trans-coronary Cooling and Dilution for Cardioprotection During Revascularisation for ST-elevation Myocardial Infarction
Official title: Trans-coronary Cooling and Dilution for Cardioprotection During Revascularisation for ST-elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Myocardial Infarction
Reperfusion Injury, Myocardial
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
First posted: 2023-11-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised placebo controlled
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

1. The study will explore the invasive haemodynamic assessment of coronary flow and microvascular function
2. The study will explore blood biomarkers before and after treatment for myocardial infarction
3. 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recruitment rate
timeFrame: 1 year
measure: Feasibility (Number of studies where all the planned measurements have been collected / total studies)
timeFrame: 1 year
measure: Safety (Adverse events should not be significantly higher in the treatment arm compared to control, nor plausibly caused by the treatment)
timeFrame: 1 year
Secondary outcomes:
measure: Index of microvascular resistance (IMR) 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Fractional flow reserve (FFR) 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Coronary flow reserve (CFR) 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Resistive reserve ratio (RRR) 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Resting full-cycle ratio (RFR) 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Intracoronary temperature change
timeFrame: 1 hour
measure: Infusion volume
timeFrame: 1 hour
measure: Infusion rate
timeFrame: 1 hour
measure: Chest pain during study infusion
timeFrame: 1 hour
measure: ECG changes during study infusion
timeFrame: 1 hour
measure: Heart rhythm changes during study infusion
timeFrame: 1 hour
measure: Myocardial blush grade 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Thrombolysis in Myocardial Infarction (TIMI) flow 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: ST segment resolution 10 mins after completion of percutaneous coronary intervention and study infusion
timeFrame: 1 hour
measure: Heart Rhythm disturbance from baseline to 12 hours
timeFrame: 12 hours
measure: Haemodynamic compromise from baseline to 12 hours
timeFrame: 12 hours
measure: Left ventricular ejection fraction (LVEF) at 48 hours
timeFrame: 2 days
measure: Left ventricular ejection fraction (LVEF) at 6 months
timeFrame: 6 months
measure: Wall motion score index (WMSI) at 48 hours
timeFrame: 48 hours
measure: Wall motion score index (WMSI) at 6 months
timeFrame: 6 months
measure: Global longitudinal strain (GLS) at 48 hours
timeFrame: 48 hours
measure: Global longitudinal strain (GLS) at 6 months
timeFrame: 6 months
measure: Length of stay
timeFrame: 3-5 days
measure: Peak high-sensitivity cardiac troponin T (hs-cTnT, ng/l)
timeFrame: 1-3 days
measure: N-terminal pro-brain natriuretic peptide (NT-proBNP, ng/l)
timeFrame: 1-3 days
measure: Interleukin-1b
timeFrame: 1 day
measure: Interleukin-1 receptor antagonist
timeFrame: 1 day
measure: Interleukin-6
timeFrame: 1 day
measure: Interleukin-10
timeFrame: 1 day
measure: First pass microvascular obstruction extent (FP MVO)
timeFrame: 1-3 days
measure: First pass microvascular obstruction extent (FP MVO) at 6 months
timeFrame: 6 months
measure: Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI, adjusted for area at-risk
timeFrame: 1-3 days
measure: Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI, adjusted for area at-risk, at 6 months
timeFrame: 6 months
measure: Late MVO (presence / absence) on LGE
timeFrame: 1-3 days
measure: Late MVO (presence / absence) on LGE at 6 months
timeFrame: 6 months
measure: Initial infarct size (LGE)
timeFrame: 1-3 days
measure: Infarct size (LGE) at 6 months
timeFrame: 6 months
measure: Initial MSI (area-at-risk minus initial infarct size/area-at-risk)
timeFrame: 1-3 days
measure: MSI (area-at-risk minus initial infarct size/area-at-risk) at 6 months
timeFrame: 6 months
measure: Left ventricular end-diastolic volume index (LVEDVI)
timeFrame: 1-3 days
measure: Left ventricular end-diastolic volume index (LVEDVI) at 6 months
timeFrame: 6 months
measure: Left ventricular end-systolic volume index (LVESVI)
timeFrame: 1-3 days
measure: Left ventricular end-systolic volume index (LVESVI) at 6 months
timeFrame: 6 months
measure: Cardiac Magnetic Resonance-based Left ventricular ejection fraction (LVEF)
timeFrame: 1-3 days
measure: Cardiac Magnetic Resonance-based Left ventricular ejection fraction (LVEF) at 6 months
timeFrame: 6 months
measure: Myocardial haemorrhage (presence/absence)
timeFrame: 1-3 days
measure: Myocardial haemorrhage (presence/absence) at 6 months
timeFrame: 6 months
measure: Myocardial haemorrhage extent (% of LV)
timeFrame: 1-3 days
measure: Myocardial haemorrhage extent (% of LV) at 6 months
timeFrame: 6 months
measure: Composite of all-cause mortality and hospitalization for heart failure at 6 weeks
timeFrame: 6 weeks
measure: Hospitalization for heart failure at 6 weeks
timeFrame: 6 weeks
measure: Cardiovascular mortality at 6 weeks
timeFrame: 6 weeks
measure: All-cause mortality at 6 weeks
timeFrame: 6 weeks
measure: Hospitalization for heart failure at 6 months
timeFrame: 6 months
measure: Cardiovascular mortality at 6 months
timeFrame: 6 months
measure: Composite of all-cause mortality and hospitalization for heart failure at 6 months
timeFrame: 6 months
measure: All-cause mortality at 6 months
timeFrame: 6 months
measure: Composite of all-cause mortality and hospitalization for heart failure at 12 months
timeFrame: 12 months
measure: Hospitalization for heart failure at 12 months
timeFrame: 12 months
measure: Cardiovascular mortality at 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Uxbridge
country: United Kingdom
facility: Harefield Hospital
Study officials:
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Miles C Dalby, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Otterspoor LC, Van 't Veer M, Van Nunen LX, Brueren GRG, Tonino PAL, Wijnbergen IF, Helmes H, Zimmermann FM, Van Hagen E, Johnson NP, Pijls NHJ. Safety and feasibility of selective intracoronary hypothermia in acute myocardial infarction. EuroIntervention. 2017 Dec 8;13(12):e1475-e1482. doi: 10.4244/EIJ-D-17-00240.
citation: McGarvey M, Ali O, Iqbal MB, Ilsley C, Wong J, Di Mario C, Redwood S, Patterson T, Pennell DJ, Rogers P, Dalby M; ORCA-3 For the Optimal Restoration of Cardiac Activity (ORCA) Group. A feasibility and safety study of intracoronary hemodilution during primary coronary angioplasty in order to reduce reperfusion injury in myocardial infarction. Catheter Cardiovasc Interv. 2018 Feb 1;91(2):234-241. doi: 10.1002/ccd.27136. Epub 2017 Jun 21.
citation: Erlinge D, Gotberg M, Lang I, Holzer M, Noc M, Clemmensen P, Jensen U, Metzler B, James S, Botker HE, Omerovic E, Engblom H, Carlsson M, Arheden H, Ostlund O, Wallentin L, Harnek J, Olivecrona GK. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol. 2014 May 13;63(18):1857-65. doi: 10.1016/j.jacc.2013.12.027. Epub 2014 Feb 5.