Clinical trial NCT04032925: The Pressure-controlled Intermittent Coronary Sinus Occlusion on VentrIcular PERformance Study
Official title: Understanding the Effects of Pressure-controlled Intermittent Coronary Sinus Occlusion Assisted Percutaneous Coronary Intervention on Coronary Physiology and Left Ventricular Performance
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myocardial Infarction
Lead sponsor: Oxford University Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: Miracor Medical SA
First posted: 2019-07-25
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The PICSO ViPER study is a prospective single centre cohort study of the use of PICSO in patients presenting acute myocardial infarction and impaired function of the left ventricle and candidate to angioplasty the left anterior descending (LAD) coronary artery.

The percutaneous coronary intervention (PCI) procedure will be undertaken in a standard fashion, in accordance with the Oxford University Hospitals NHS Trust (OUHT) departmental guidelines for PCI, and includes the use of pressure wire measurements before and after stent deployment. PICSO treatment will be added on top of the conventional treatment.

The protocol will constitute of 5 main stages (that will all be performed during index angioplasty procedure). The protocol is complete at the end of the angioplasty procedure, and the patient will exit the study at this point. The five stages of the protocol are described below (for details see "Detailed Description"):

* Baseline
* PICSO treatment during pre-dilation
* Stenting with PICSO support
* Post-stent Physiology
* PICSO treatment during post-dilation

Detailed description: In detail, the five stages of the PICSO VIPER study include:

Stage 1: Baseline

* Diagnostic angiography will be performed in the standard manner using appropriate catheters.
* Pre-stenting coronary physiology parameters, namely fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) will be measured, using a pressure wire, as used for routine clinical measurements in patients undergoing PCI.
* Via a separate arterial access, a conductance catheter will be inserted retrogradely in the left ventricle for baseline measurements of cardiac pump function .
* Baseline blood samples will be withdrawn from the CS (via PICSO balloon) and ascending aorta (via coronary guiding catheter used for revascularization)

Stage 2: PICSO treatment during pre-dilation

* The PICSO device will be deployed as already previously described in the literature.
* Pre-dilation will be performed using an angioplasty balloon at a size determined by the operator, as per standard clinical practice. Balloon will be maintained inflated for a minimum of 1 minute to a maximum of 2 minutes if well tolerated by the patient.
* Balloon inflation will be performed once with the PICSO device activated and once with PICSO device in standby. The order of this will be determined by randomisation via Sequentially Numbered Opaque Sealed Envelopes.
* During each balloon inflation measurements of coronary and cardiac function will be performed and blood samples will be collected exactly as in stage 1.

Stage 3: Stenting with PICSO support

• Stenting is performed as usual clinical practice while the PICSO device is active. The overall duration of PICSO will be no less than 20 minutes, up to a maximum of 45 minutes.

Stage 4: Post-stent Physiology

* Post-stenting coronary and cardiac physiology parameters will be measured using a pressure wire and conductance catheter, respectively.
* Blood samples will be drawn from the CS and the coronary guide catheter as described in stage 1.

Stage 5

* Stent post-dilation will be performed using an angioplasty balloon at a size determined by the operator, as per standard clinical practice. Balloon will be maintained inflated for a minimum of 1 minute to a maximum of 2 minutes if well tolerated by the patient.
* Balloon inflation will be performed in all patients once with the PICSO device activated and once with the PICSO device in standby. The order of this will be the same as in Stage 2 (as determined by Sequentially Numbered Opaque Sealed Envelopes)
* During each balloon inflation measurements will be made of coronary and cardiac physiology parameters and blood samples will be drawn from the CS and the coronary guide catheter as described in stage 1.
* Following this, the participant completes and exits the study.

Eligibility criteria: Inclusion Criteria:

* Admission with NSTEMI and considered for coronary angiogram for a view for PCI
* Echocardiographic evidence of at least mild left ventricular systolic impairment (Ejection Fraction \< 50%) or regional wall motion abnormalities in LAD territory
* Angiographically proven stenosis of the LAD treated with PCI

Exclusion Criteria:

* Patient referred for surgical revascularization or considered for medical management of coronary disease
* Planned revascularization by mean of balloon angioplasty without stenting
* Patients in whom safety or clinical concerns preclude participation. These would include:

  * Significant left main stem disease
  * Cardiogenic shock and/or haemodynamic instability at the time of enrolment/screening
* Recent PCI or admission with acute coronary syndrome in the previous 3 months before screening/enrolment
* Known anaemia (Hb \< 90 g/L)
* Pregnant or breast-feeding females
* History of stroke, TIA or reversible ischaemic neurological disease within last 6 months
* Known severe renal failure (eGFR \< 30 ml/min/1.73m2) or history of dialysis or renal transplant
* Previous coronary bypass artery grafting
* Previous PCI to LAD
* Known severe valvular abnormalities
* Use of warfarin
* Presence of pacemaker electrode or medical device in the coronary sinus
* History of inability or, in the opinion of the investigator, anticipated inability to tolerate pharmacologic stress testing (e.g. second- or third-degree AV block without a cardiac pacemaker, severe asthma, resting systolic blood pressure \<90mmHg, unstable coronary disease, use of medications which may interfere with the test).
* Unwilling, or unable, to give informed consent.

Primary outcomes:
measure: End-systolic pressure volume relationship (ESPVR)
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: End diastolic pressure volume relationship (EDPVR)
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Minimum dp/dt
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Maximum dp/dt
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Tau
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Stroke work
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Pressure-Volume Area (PVA)
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Cardiac Efficiency
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Secondary outcomes:
measure: Transcoronary gradient of lactates levels
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Transcoronary oxygen content
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Transcoronary microRNA gradient
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other outcomes:
measure: Measurement of IMR
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Measurement of CFR
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Measurement of Coronary wedge pressure during balloon occlusion.
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Time for PICSO deployment
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Screening time for PICSO deployment
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Radiation dose for PICSO deployment
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Rate of coronary sinus perforation
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Rate of coronary sinus dissection
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Rate of coronary sinus thrombosis
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
measure: Rate of PICSO failure deployment
timeFrame: At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Locations:
city: Oxford
country: United Kingdom
facility: Oxford Heart Centre
Study officials:
affiliation: Oxford University Hospitals - NHS Foudation Trust
name: Giovanni Luigi De Maria, MD, PhD
role: STUDY_CHAIR
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