Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion
Condition: ST Elevation Myocardial Infarction
MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction
Study type: Interventional

Summary: 
      The OxAMI-PICSO is a study about the use of pressure controlled intermittent coronary sinus
      occlusion (PICSO) to improve the treatment of patients presenting with heart attack. PICSO is
      a device consisting of a balloon which is deployed in the coronary sinus. When inflated the
      balloon can improve the blood flow to the region of heart affected by the heart attack. The
      study aims to analyse the potential benefit of PICSO in improving blood flow to heart muscle
      in a selected group of patients admitted with a large heart attack involving the anterior
      wall of the heart. The comparator group will be a well-matched group of participants of the
      ongoing OxAMI study.

      In order to select patients with a large heart attack, we will measure the index of
      microcirculatory resistance (IMR), before completion of the heart attack treatment procedure.
      The IMR value provides measurement of the blood flow at the level of the tiny vessels
      branching from the large coronary arteries. Our preliminary data from the OxAMI study have
      shown that an IMR > 40 suggests that the patient is having a large myocardial infarction
      (heart attack). Only patients with starting IMR > 40 will be considered eligible for the
      PICSO treatment.

      The benefit of PICSO will be assessed by measuring 1) indexes of coronary blood flow, 2) the
      extension of the infarcted area and 3) the levels of different molecules released in the
      blood.
    

Detailed description: 
      The OxAMI-PICSO study is a prospective single centre observational cohort study of the use of
      pressure-control intermittent coronary sinus occlusion (PICSO) in patients presenting for
      primary percutaneous coronary intervention (PCI) for acute myocardial infarction.

      Patients, age 30-90, presenting with ST elevation myocardial infarction will be considered
      for inclusion in the study. Measurement of index of microcirculatory resistance (IMR) before
      stenting is an essential prerequisite for the study: only patients with pre-stenting IMR > 40
      will be considered eligible for the PICSO treatment. Patients with IMR≤ 40 will remain in the
      study but will not undergo PICSO treatment.

      The procedure for consent in patients undergoing emergency PCI will be as already established
      in the ongoing OxAMI study (Ethics Ref 11/SC/0397) Because of the urgency of the situation it
      is not feasible to obtain fully informed written consent. Fully informed consent requires
      that the potential participant have time to read and reflect on a patient information sheet
      which in this context is clinically inadvisable. We therefore propose to obtain verbal assent
      so as to optimize the amount of appropriate information conveyed to potential participants
      acutely and minimize the clinical risks involved with substantial delay. The research study
      will be discussed verbally with the patient and the risks and benefits explained. Only
      conscious patients, able to provide verbal assent will be enrolled in the study.

      In detail the patient at the time of verbal assent process will be informed that as part of
      the research project he/she might undergo to measurement of the index of microcirculatory
      resistance (IMR) which allows to have an indirect assessment of the entity of the ongoing
      heart attack. The patient will be also informed that in case IMR value will be greater than
      40, thus suggesting a possible significant damage to the heart muscle that may benefit from
      additional treatment, he/she might be asked to provide assent for PICSO treatment. Patients
      with pre-stenting IMR ≤ 40 or those with pre-stenting IMR > 40 who elect not to receive PICSO
      treatment will be given the opportunity to continue to participate within the OxAMI-PICSO
      study, but without the use of the PICSO device.

      Participants will be reminded that they have the right to withdraw from the study at any
      stage and that this will not affect their treatment or human rights. Once the emergency phase
      is over and treatment has been delivered, full written informed consent will be sought as
      soon as practical. For most patients this means within 12 hours of admission.

      The PCI procedure will be undertaken in a standard fashion, and include the use of pressure
      wire measurements before and after stent deployment.

      Only patients with pre-stenting IMR > 40 and who assent to receive PICSO treatment will
      undergo 24 hours coronary angiogram with coronary physiology measurement, 24-48 hours CMR
      scan and 6 months CMR scan. Patients who assent to participate in the study but in whom the
      pre-stenting IMR ≤ 40, or those in whom the pre-stenting IMR > 40 but the participant
      declines PICSO treatment will remain in the study for clinical data collection only at the
      same follow up time points (24 hours, 48 hours and 6 months).

      The control group of the OxAMI-PICSO study will be represented by a matched cohort of
      patients with STEMI with pre-stenting IMR greater than 40 units already enrolled as part of
      the OxAMI study (Ethics Ref 11/SC/0397)

      In details the OxAMI-PICSO study will consist of five stages:

      Stage 1: Pre-Stenting

        1. Diagnostic angiography will be performed in the standard manner using appropriate
           catheters.

        2. Bivalirudin will be administered (0.75mg/kg bolus followed by an infusion of 1.75
           mg/kg/min for up 4 hours after the procedure as clinically warranted), as routinely used
           for PCI. The lesion will be crossed with a coronary guide wire in the usual manner for
           PCI. Normal blood flow will be rapidly achieved by thrombus aspiration and/or
           predilation

        3. Pre-stenting IMR will be measured, using a pressure wire, as used for routine clinical
           measurements in patients undergoing PCI.

        4. If pre-stenting IMR is > 40, patients will be invited to receive the PICSO device. If
           pre-stenting IMR is ≤ 40 PICSO device will not be proposed, but the patient will be
           invited to remain in the study for routine clinical data collection.

      Stage 2: PICSO treatment

      1. In patients with IMR >40 who assent to PICSO treatment, the PICSO device will be deployed
      and PICSO treatment delivered until a PICSO dose of 800 mmHg is achieved

      Stage 3: Stenting

        1. Stenting is performed as usual clinical practice.

        2. Post-dilation is left to operator's discretion, as in clinical routine.

        3. At the end of the procedure a final reassessment of IMR is performed again as previously
           described.

      Stage 4: 24-48 hours post PCI

      Full written consent to take part to the OxAMI-PICSO study is obtained as soon as
      practicable. The following study assessments may be carried out:

        1. Repeat coronary angiogram for assessment of coronary physiology parameters assessment -
           for participants who receive the PICSO device only

        2. Cardiac magnetic resonance - for participants who receive the PICSO device only

        3. Data Collection, Patient Reported Outcomes and Cardiovascular Outcomes

      Stage 5: 6 months post PCI Participants will be invited to attend the hospital as an
      outpatient at approximately 6 months post-PPCI for the following research assessments

        1. Cardiovascular MRI - for participants who receive the PICSO device only

        2. Data Collection, Patient Reported Outcomes and Cardiovascular Outcomes

      Recruitment to the study will cease as soon as 25 participants have undergone PICSO treatment
      and have completed follow-up at 6 months. The study will end on the date of the last CMR at 6
      months follow up of the last participant recruited.

      Sample Size

      The OxAMI-PICSO study aims to investigate the potential benefit of PICSO in a highly selected
      population of STEMI patients. In line with the data reported by Sayeed et al in a previous
      metanalysis on 7 studies about PICSO application in animal models, the recently published
      Prepare-RAMSES study also observed a 30% reduction in IS in the treatment arm, however such
      reduction was not statistically significant in comparison to the control arm. The study,
      however could still show a benefit of PICSO in terms of IS reduction at six months follow up
      in the subgroup of patients receiving high PICSO quantity. The study, however, was
      significantly hampered by the inclusion of relative low risk patients and by a small sample
      size. The author managed indeed to deliver full PICSO treatment only in 63% of the initial
      planned cohort (12 patients, of the 30 planned, received a prolonged treatment with PICSO).

      In order to address the first limitation of the Prepare-RAMSES study, OxAMI-PICSO study will
      select patients with a pre-stenting higher IMR. In this way PICSO is meant to be applied only
      in a population at higher risk and highly likely to get benefit from its application.

      In this regard assuming that the stricter inclusion criteria may allow to detect a
      substantial benefit from PICSO compared to the control group and expecting that this will
      allow to achieve a significant 29% reduction in IS as shown in Sayeed's metanalysis, we
      initially calculated a final sample size of 12 patients with complete final data per each
      group with an interval of confidence at 95% and a 80% power. However, considering that this
      was the final same sample size enrolled in the Prepare-RAMSES study, initially meant to
      recruit 30 patients per arm, we propose to double the actual sample size from 12 to 25 per
      arm.

      Allowing for participants who do not wish to undergo repeat cardiac catheterisation, or
      cardiac MRI, we anticipate that approximately 75 patients may be recruited to the study in
      order to achieve full participation and complete follow up in 25 subjects.
    

Intervention name(s): PICSO
Intervention type(s): Device
Intervention description(s): The PICSO Impulse catheter is a 8F double lumen catheter with a 15.5x20mm long balloon at the distal end. The balloon inflates and deflates cyclically once deployed in the coronary sinus, leading to intermitted coronary sinus pressure increase. The catheter is connected to the console through two pneumatic tubes in which helium is shuttled to and from the balloon. In addition, the coronary sinus pressure is monitored through the center lumen of the catheter.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment