Postprocedural Contrast Mediated FFR Plus Intracoronary Infusion of Nitroglycerin in Multivessel Patients (PROMETEUS TRIAL)

Postprocedural Contrast Mediated FFR Plus Intracoronary Infusion of Nitroglycerin in Multivessel Patients

the use of pressure wires is the standar of care to evaluate angiographically intermediate coronary lesions, however, limitations in the management of these type of lesions continue to be a challenge for the interventional cardiologist. The use of FFR has some limitations such as the use of adenosine due to its cost, adverse effects (e.g. transient atrioventricular block, angina, headache, etc.), time consuming and some relative contraindications for its use. In this sense, in recent years new rest indices (iFR, RFR, dPR) and hyperemic indices without adenosine (cFFR-NTG, Pd/Pa-NTG or cFFR) have been developed, demonstrating an improvement in terms of outcomes with its use, so they can also be used as a tool to guide us to plan our strategy. These new indices, particularly the cFFR-NTG, are simpler, at least as safe and have an excellent correlation with the FFR with adenosine in the assessment of intermediate coronary lesions.

In recent years, functional assessment after intervention has also been increasingly implemented, which, like intracoronary imaging, can make us change our attitude and correlate with the prognosis. The lower implementation of this practice, especially in multivessel patients, may result from having to lose the position of the wire to check equalization, difficulty in crossing the wire, wear/breakage of the material after diagnosis (2-3 vessels), use more time and contrast, etc. These problems could be reduced, at least partially, with the use of the workhorse coronary guidewire pressure microcatheter to measure post-PCI functional assessment. Although the usefulness of post-PCI FFR has been demonstrated, there is no clearly established cut-off value (0.84-0.96) and it seems that in reality the values are a continuum of risk so that the higher the value, the better the prognosis . Furthermore, other simpler indices such as rest or hyperemic indices without adenosine have not been correlated with FFR in post-PCI.

The purpose of this study is to evaluate the correlation between cFFR-NTG and other indices taking FFR as a reference in multivessel patients after undergoing intervention. Establish cut-off points and correlate it with adverse cardiovascular events (MACE) in a 1-year clinical follow-up.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Disease
• Intervention / Treatment: Diagnostic test: Fractional Flow Reserve

Detailed Description

Percutaneous coronary intervention (PCI) is a standard treatment strategy for coronary artery disease (CAD). With the presence of myocardial ischemia, PCI reduces the risks of death, myocardial infarction (MI), and revascularization compared to medical therapy. However, the risk of future clinical events remains high, and about 10% of patients experienced further cardiovascular events after PCI. Facing intermediate coronary lesions the use of pressure wires is the standar of care, however, limitations in the management of angiographically intermediate coronary lesions continue to be a challenge for the interventional cardiologist. The measurement of fractional flow reserve (FFR) to determine the hemodynamic relevance of coronary stenosis has been shown to be a technique that improves the prognosis and cost-efficiency of the procedures when compared to visual angiographic interpretation alone. Due to this evidence, the use of FFR to guide interventional procedures is a class I recommendation in current clinical practice guidelines.

Patients with multivessel coronary artery disease are another field in the use of pressure guiding. In these patients, the use of FFR has demonstrated the reclassification of the severity of coronary lesions in up to 40% of cases, modifying the number of functionally significant lesions and making it possible to reorient therapeutic decisions, avoiding interventional treatment of non-significant lesions and with a better prognosis.

However, the use of FFR has some limitations such as the use of adenosine due to its cost, adverse effects (e.g. transient atrioventricular block, angina, headache, etc.) and time consuming. In addition, the presence of atrioventricular block, asthma or severe chronic obstructive pulmonary disease are relative contraindications for its use. In this sense, in recent years new rest indices (iFR, RFR, dPR) and hyperemic indices without adenosine (cFFR-NTG, Pd/Pa-NTG or cFFR) have been developed , demonstrating an improvement in terms of outcomes with its use, so they can also be used as a tool to guide us to plan our strategy. These new indices, particularly the cFFR-NTG, are simpler, at least as safe and have an excellent correlation with the FFR with adenosine in the assessment of intermediate coronary lesions.

In recent years, functional assessment after intervention has also been increasingly implemented, which, like intracoronary imaging, can make us change our attitude and correlate with the prognosis. The lower implementation of this practice, especially in multivessel patients, may result from having to lose the position of the wire to check equalization, difficulty in crossing the wire, wear/breakage of the material after diagnosis (2-3 vessels), use more time and contrast, etc. These problems could be reduced, at least partially, with the use of the workhorse coronary guidewire pressure microcatheter to measure post-PCI functional assessment. Although the usefulness of post-PCI FFR has been demonstrated, there is no clearly established cut-off value (0.84-0.96) and it seems that in reality the values are a continuum of risk so that the higher the value, the better the prognosis . Furthermore, other simpler indices such as rest or hyperemic indices without adenosine have not been correlated with FFR in post-PCI.

The purpose of this study is to evaluate the correlation between cFFR-NTG and other indices taking FFR as a reference in multivessel patients after undergoing intervention. Establish cut-off points and correlate it with adverse cardiovascular events (MACE) in a 1-year clinical follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: FUNDACION EPIC; Phone Number: 0034987876135; Email: iepic@fundacionepic.org
• Study Contact Backup: Name: SANTIAGO J CAMACHO FREIRE, MD, PhD; Phone Number: 0034677981941; Email: hemodinamica.cardiologia.huelva@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients >18 years old and,
• Patients with multivessel coronary artery disease (multivessel coronary artery disease will be considered the presence of significant stenosis in 2 or more first or second order vessels greater than 1.5 mm in diameter with an angiographic reduction of their diameter ≥50% by visual estimation) subsidiary of percutaneous coronary revascularization in at least one of them and,
• Use of Navvus pressure microcatheter both for functional diagnosis and for post-PCI evaluation of the different vessels and,
• Patients who have signed the Informed Consent.

Exclusion Criteria:

• Patients with intolerance or contraindication to adenosine.
• Hemodynamically unstable patients, acute phase of a STEACS.
• Patient with significant comorbidity with limited life expectancy.
• Patients with the patient's express refusal to participate in the study.
• Pregnant or breastfeeding female patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Percutaneous coronary intervention (PCI) and guide wire post PCI in multivessel patients

Diagnostic test: Fractional Flow Reserve; Agreement measurements between the different post-ICP functional values (cFFR+NTG and FFR) will be performed at the end of the intervention on the treated vessels. The study protocol consists of 4 sequential steps (separated by at least 30 sec): Determination of FFR with contrast and NTG: cFFR +NTG will be calculated with the lowest ratio after the infusion of 0.2 mg bolus of intracoronary NTG and pushed with contrast.; Determination of distal pressure between basal aortic pressure: The Pd/Pa will be obtained after about 30-60 seconds of the NTG bolus in step 1.; Determination of the diastolic dPR index: the average value (2-3 determinations).; Determination of fractional flow reserve with adenosine: The FFR will be obtained after continuous peripheral venous infusion with adenosine or with intracoronary boluses according to the protocol of each center.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement between cFFR+NTG and FFR	To evaluate the agreement between cFFR+NTG and FFR after successful angiographic revascularization of lesions in multivessel patients.	Index Procedure
SAFETY: MACE	To evaluate the safety associated with performing PCI in multivessel patients with a pre- and post-PCI functional study in terms of MACE at 12 months that includes: Cardiovascular death, Acute myocardial infarction of the lesion treated/functionally evaluated, Need for revascularization of the treated/functionally evaluated lesion.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular death	Cardiovascular death	12 months
Agreement between Pd/Pa or dPR and FFR	To evaluate the agreement between Pd/Pa or dPR and FFR after successful angiographic revascularization of lesions in multivessel patients, with a cut-off point of FFR ≥0.80.	Index Procedure
Cut-off point for cFFR+NTG post-ICP	Determine a cut-off point for cFFR+NTG post-ICP.	Index Procedure
Evaluate the change in strategy that the measurement of FFR values ≤0.90 post-PCI	Evaluate the change in strategy that the measurement of FFR values ≤0.90 post-PCI may entail: use of intracoronary imaging techniques, post-dilation, etc.	Index Procedure
Cardiac death	Cardiac death	12 months
Acute myocardial infarction of the lesion treated/functionally evaluated	Acute myocardial infarction of the lesion treated/functionally evaluated	12 months
Acute myocardial infarction from any lesion	Acute myocardial infarction from any lesion	12 months
Need for revascularization of the lesion treated/functionally evaluated	Need for revascularization of the lesion treated/functionally evaluated	12 months
Need for revascularization of any lesion	Need for revascularization of any lesion	12 months

Collaborators and Investigators

• Sponsor: Fundación EPIC

Publications and helpful links

General Publications

• van Nunen LX, Zimmermann FM, Tonino PA, Barbato E, Baumbach A, Engstrom T, Klauss V, MacCarthy PA, Manoharan G, Oldroyd KG, Ver Lee PN, Van't Veer M, Fearon WF, De Bruyne B, Pijls NH; FAME Study Investigators. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. 2015 Nov 7;386(10006):1853-60. doi: 10.1016/S0140-6736(15)00057-4. Epub 2015 Aug 30.
• Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165.
• Gutierrez-Barrios A, Noval-Morillas I, Camacho-Freire S, Puche JE, Gheorghe L, Silva E, Alarcon-Lastra I, Canadas-Pruano D, Gomez-Menchero A, Calle-Perez G, Diaz-Fernandez JF, Vazquez-Garcia R. Contrast FFR plus intracoronary injection of nitro-glycerine accurately predicts FFR for coronary stenosis functional assessment. Minerva Cardiol Angiol. 2021 Aug;69(4):449-457. doi: 10.23736/S2724-5683.20.05354-2. Epub 2020 Dec 1.
• Patel MR, Jeremias A, Maehara A, Matsumura M, Zhang Z, Schneider J, Tang K, Talwar S, Marques K, Shammas NW, Gruberg L, Seto A, Samady H, Sharp ASP, Ali ZA, Mintz G, Davies J, Stone GW. 1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial. JACC Cardiovasc Interv. 2022 Jan 10;15(1):52-61. doi: 10.1016/j.jcin.2021.09.042.
• Thakur U, Khav N, Comella A, Michail M, Ihdayhid AR, Poon E, Nicholls SJ, Ko B, Brown AJ. Fractional Flow Reserve following Percutaneous Coronary Intervention. J Interv Cardiol. 2020 Jun 5;2020:7467943. doi: 10.1155/2020/7467943. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Estimated): March 20, 2024
• Primary Completion (Estimated): January 20, 2025
• Study Completion (Estimated): January 20, 2026

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Fractional Flow Reserve; Percutaneous Coronary Intervention (PCI)
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease
• Other Study ID Numbers: EPIC35-PROMETEUS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No