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

Overview

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.

Interventions

• Other Transcoronary cooling and dilution
  Transcoronary cooling and dilution
• Other Standard of care
  Routine clinical care

Primary outcome measures

• Recruitment rate [Time frame: 1 year]
• Feasibility (Number of studies where all the planned measurements have been collected / total studies) [Time frame: 1 year]
• 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]

Secondary outcome measures (12)

• Index of microvascular resistance (IMR) 10 mins after completion of percutaneous coronary intervention and study infusion [Time frame: 1 hour]
• Fractional flow reserve (FFR) 10 mins after completion of percutaneous coronary intervention and study infusion [Time frame: 1 hour]
• Coronary flow reserve (CFR) 10 mins after completion of percutaneous coronary intervention and study infusion [Time frame: 1 hour]
• Resistive reserve ratio (RRR) 10 mins after completion of percutaneous coronary intervention and study infusion [Time frame: 1 hour]
• Resting full-cycle ratio (RFR) 10 mins after completion of percutaneous coronary intervention and study infusion [Time frame: 1 hour]
• Intracoronary temperature change [Time frame: 1 hour]
• Infusion volume [Time frame: 1 hour]
• Infusion rate [Time frame: 1 hour]
• Chest pain during study infusion [Time frame: 1 hour]
• ECG changes during study infusion [Time frame: 1 hour]
• Heart rhythm changes during study infusion [Time frame: 1 hour]
• Myocardial blush grade 10 mins after completion of percutaneous coronary intervention and study infusion [Time frame: 1 hour]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• Harefield Hospital — Uxbridge

Publications

• 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. PMID 28829744
• 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. do PMID 28636165
• 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 c PMID 24509284
• Carulli E, McGarvey M, Chabok M, Panoulas V, Rosser G, Akhtar M, Smith R, Chandra N, Al-Hussaini A, Kabir T, Barker L, Bruno F, Konstantinou K, de Silva R, Hill J, Xu Y, Lane R, Bucciarelli-Ducci C, Luescher T, Dalby M. Transcoronary cooling and dilution for cardioprotection during revascularisation for ST-segment elevation myocardial infarction: Design and rationale of the STEMI-Cool study. Am He PMID 39742936

Identifiers

NCT: NCT06128993 · 315559

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗