The Pressure-controlled Intermittent Coronary Sinus Occlusion on VentrIcular PERformance Study

Myocardial Infarction Clinical Trial

— PICSO-ViPER  

Official title:

Understanding the Effects of Pressure-controlled Intermittent Coronary Sinus Occlusion Assisted Percutaneous Coronary Intervention on Coronary Physiology and Left Ventricular Performance

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04032925
• Other study ID #: 14338
• Status: Terminated
• Phase: Phase 2
• Start date: August 3, 2021
• Est. completion date: December 29, 2022

Study information

• Verified date: August 2023
• Source: Oxford University Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: December 29, 2022
• Est. primary completion date: December 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Device:
• PICSO
PICSO therapy is delivered through the PICSO Impulse System, which consists of the PICSO Impulse console and PICSO impulse catheter. The PICSO therapy is delivered in each patient for a minimum of 20 minutes to a maximum of 45 minutes. The PICSO Impulse catheter is automatically activated by the PICSO Impulse console. It is inserted in the coronary sinus via femoral vein access. The PICSO Impulse Console cyclically inflates and deflates the balloon at the tip of the PICSO Impulse catheter, generating transient increase in coronary sinus pressure.

Locations

Country	Name	City	State
United Kingdom	Oxford Heart Centre	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
Oxford University Hospitals NHS Trust	Miracor Medical SA

Country where clinical trial is conducted

United Kingdom, 

References & Publications (13)

De Maria GL, Alkhalil M, Borlotti A, Wolfrum M, Gaughran L, Dall'Armellina E, Langrish JP, Lucking AJ, Choudhury RP, Kharbanda RK, Channon KM, Banning AP. Index of microcirculatory resistance-guided therapy with pressure-controlled intermittent coronary sinus occlusion improves coronary microvascular function and reduces infarct size in patients with ST-elevation myocardial infarction: the Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion study (OxAMI-PICSO study). EuroIntervention. 2018 Jun 8;14(3):e352-e359. doi: 10.4244/EIJ-D-18-00378. — View Citation

Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev. 2008 Jul;88(3):1009-86. doi: 10.1152/physrev.00045.2006. — View Citation

Ido A, Hasebe N, Matsuhashi H, Kikuchi K. Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1361-7. doi: 10.1152/ajpheart.2001.280.3.H1361. — View Citation

Kirtane AJ, Moses JW. Revascularization in heart failure: the role of percutaneous coronary intervention. Heart Fail Clin. 2007 Apr;3(2):229-35. doi: 10.1016/j.hfc.2007.05.003. — View Citation

Lazar HL, Rajaii A, Roberts AJ. Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion. J Thorac Cardiovasc Surg. 1988 Apr;95(4):637-42. — View Citation

Lazar HL. Advantages of pressure-controlled intermittent coronary sinus occlusion over left ventricle-powered coronary sinus retroperfusion. Ann Thorac Surg. 2001 Jan;71(1):402. doi: 10.1016/s0003-4975(00)02036-1. No abstract available. — View Citation

Martin JS, Byrne JG, Ghez OY, Sayeed-Shah U, Grachev SD, Laurence RG, Cohn LH. LV-powered coronary sinus retroperfusion reduces infarct size in acutely ischemic pigs. Ann Thorac Surg. 2000 Jan;69(1):84-9. doi: 10.1016/s0003-4975(99)00865-6. — View Citation

Martinez GJ, Yong AS, Fearon WF, Ng MK. The index of microcirculatory resistance in the physiologic assessment of the coronary microcirculation. Coron Artery Dis. 2015 Aug;26 Suppl 1:e15-26. doi: 10.1097/MCA.0000000000000213. — View Citation

Mohl W, Mina S, Milasinovic D, Kasahara H, Wei S, Maurer G. Is activation of coronary venous cells the key to cardiac regeneration? Nat Clin Pract Cardiovasc Med. 2008 Sep;5(9):528-30. doi: 10.1038/ncpcardio1298. No abstract available. — View Citation

Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurheartj/ehy394. No abstract available. Erratum In: Eur Heart J. 2019 Oct 1;40(37):3096. — View Citation

Spaan JA. Mechanical determinants of myocardial perfusion. Basic Res Cardiol. 1995 Mar-Apr;90(2):89-102. doi: 10.1007/BF00789439. No abstract available. — View Citation

van de Hoef TP, Nijveldt R, van der Ent M, Neunteufl T, Meuwissen M, Khattab A, Berger R, Kuijt WJ, Wykrzykowska J, Tijssen JG, van Rossum AC, Stone GW, Piek JJ. Pressure-controlled intermittent coronary sinus occlusion (PICSO) in acute ST-segment elevation myocardial infarction: results of the Prepare RAMSES safety and feasibility study. EuroIntervention. 2015 May;11(1):37-44. doi: 10.4244/EIJY15M03_10. — View Citation

Van de Hoef TP, Nolte F, Delewi R, Henriques JP, Spaan JA, Tijssen JG, Siebes M, Wykrzykowska JJ, Stone GW, Piek JJ. Intracoronary hemodynamic effects of pressure-controlled intermittent coronary sinus occlusion (PICSO): results from the First-In-Man Prepare PICSO Study. J Interv Cardiol. 2012 Dec;25(6):549-56. doi: 10.1111/j.1540-8183.2012.00768.x. Epub 2012 Sep 20. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Measurement of IMR	Coronary microvascular function	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Measurement of CFR	Coronary microvascular function	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Measurement of Coronary wedge pressure during balloon occlusion.	Coronary microvascular function	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Time for PICSO deployment	Safety Endpoint rate of coronary sinus complications: perforation, dissection, thrombosis; time for PICSO deployment / screening time and radiation dose	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Screening time for PICSO deployment	Safety Endpoint rate of coronary sinus complications: perforation, dissection, thrombosis; time for PICSO deployment / screening time and radiation dose	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Radiation dose for PICSO deployment	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Rate of coronary sinus perforation	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Rate of coronary sinus dissection	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Rate of coronary sinus thrombosis	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Other	Rate of PICSO failure deployment	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	End-systolic pressure volume relationship (ESPVR)	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	End diastolic pressure volume relationship (EDPVR)	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	Minimum dp/dt	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	Maximum dp/dt	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	Tau	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	Stroke work	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	Pressure-Volume Area (PVA)	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Primary	Cardiac Efficiency	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Secondary	Transcoronary gradient of lactates levels	Cardiac metabolism and energetics	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Secondary	Transcoronary oxygen content	Cardiac metabolism and energetics	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Secondary	Transcoronary microRNA gradient	Cardiac metabolism and energetics	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)