Reassessment of myocardIAL Bridge TOwards PeRsOnalized Medicine (RIALTO PRO)

July 9, 2024 updated by: Domenico D'Amario, Azienda Ospedaliero Universitaria Maggiore della Carita

Reassessment of myocardIAL Bridge TOwards PeRsOnalized Medicine: RIALTO PRO

The "RIALTO-PRO" study aims to optimize the diagnostic and therapeutic algorithm for myocardial bridge (MB) patients, testing the diagnostic value of a full invasive diagnostic procedure, and, consequently, the prognostic value of a tailored approach. the study objective is to determine the diagnostic and prognostic value of a full-physiology approach strategy versus a standard approach strategy in patients with a MB.

The "RIALTO PRO" study is a randomized, multicentre, prospective, open-label, superiority trial comparing a personalised versus standard management in patients with MB. Consenting and eligible patients will be randomised 1:1 to either a "full-physiology approach", consisting of a comprehensive diagnostic algorithm aimed at unmasking the main pathophysiological mechanism of myocardial ischemia and consequently a tailored treatment, or a "standard approach", consisting of angiographic evaluation of the tunnelled segment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

TRIAL PROCEDURES Once MB is angiographically detected, eligible and consenting patients will be randomly assigned in a 1:1 ratio to receive a "standard approach" or a "full-physiology approach" during index CA.

Index coronary angiography Coronary angiography will be performed through a radial or femoral approach. Unfractionated heparin (initial weight-adjusted intravenous bolus of 50-70 IU/kg, with repeat boluses to achieve an activated clotting time ∼250) will be administered in all patients. To fully expose all segments of the coronary arteries, at least 2 perpendicular projections for the right coronary artery (RCA) and 4 projections for the LAD will be taken. Intracoronary nitrates can be used (depending on blood pressure and, in any case, at the discretion of the Investigator) to increase the angiographic sensitivity in detecting the "milking effect".

Physiological epicardial and microvascular assessment MB hemodynamic assessment will be performed using a diagnostic guidewire placed in the index vessel. Intravenous heparin (50-70 U/kg) should be administered to achieve therapeutic anticoagulation (activated clotting time ∼250 s). The innovative Abbott PressureWire™ X Guidewire will be used to measure pressure and temperature. The guidewire's wireless measurements are connected to an advanced platform (Coroventis‡ CoroFlow‡ Cardiovascular System) to measure physiological indices. Abbott's PressureWire™ X Guidewire and Coroventis‡ CoroFlow‡ Cardiovascular System are, nowadays, the only solution for the cath lab able to assess both epicardial vessel (i.e., FFR< 0.80) and microcirculation (i.e., CFR< 2.0 and IMR≥ 25).

Epicardial assessment will include:

  • Resting Pd/Pa (n.v. > 0.92)
  • FFR after intravenous adenosine administration (n.v. > 0.80)
  • RFR (n.v. > 0.89)
  • FFR after intravenous dobutamine administration (n.v. > 0.75) FFR is defined as the mean distal pressure (Pd)/mean aortic pressure (Pa) across MB during maximal hyperemia, achieved by administration of intravenous (140 μg/kg/min) or intracoronary bolus (up to 200 µg) of adenosine. Pd/Pa was automatically calculated by current computational software as the ratio found in the pressure recording. A cut-off of 0.80 will be used to detect hemodynamic relevance. Inotropic stimulation to exalt the hemodynamic significance of MB will be performed with intravenous dobutamine infusion, in case of a negative functional assessment (Pd/Pa> 0.92, FFR> 0.80, RFR> 0.89). The infusion will be started at 5 μg/kg/min and increased by 5μg/kg/min every 5 minutes up to 20 μg/kg/min or until the patient develops symptoms or clear evidence of ischemia. An intravenous infusion of 1 mg atropine will be administered if the patient will not experience symptoms or signs of myocardial ischemia with 20 μg/kg/min of dobutamine infusion. An intravenous bolus of β-blocker (i.e., metoprolol 5 mg) will be administered at the end of the procedure to antagonize the effects of dobutamine.

Microvascular assessment will include:

  • basal CFR (n.v. ≥ 2.0) and CFR after intravenous dobutamine administration (CFR-d)
  • basal IMR (n.v. < 25) and IMR after intravenous dobutamine administration (IMR-d) The coronary flow reserve and the microcirculatory resistance will be calculated using thermodilution thanks to the PressureWire™ X Guidewire. The thermodilution-based CFR cut-off value is 2.0. It is the ratio of the maximal or hyperemic flow down a coronary vessel to the resting flow. IMR is calculated as the product of distal coronary pressure at maximal hyperaemia multiplied by the hyperaemic mean transit time. Reduced CFR (< 2.0) and increased IMR (≥ 25) are representative of structural microvascular dysfunction (impaired endothelium-independent vasodilatation).

ACH provocative test In order to unmask MB-related epicardial and/or microvascular CAS, ACH provocative test will be performed in case of absence of epicardial hemodynamic significance and structural microvascular dysfunction. Incremental doses of 20, 50, 100 and 200 μg of ACH will be infused over a period of 2 minutes into the index vessel (vessel with angiographic "milking effect") via the angiographic catheter, repeating CA after each Ach dose. The test will be performed with a continuous monitoring of symptoms, electrocardiogram (ECG), and angiographic evidence of spasm. Angiographic responses during the provocation test will be assessed in multiple orthogonal views to detect the artery spasm. If either complications and/or a positive response occurred, the test will be discontinued, and higher doses will be not administered. The test will be considered positive for epicardial CAS in the presence of focal or diffuse epicardial coronary diameter reduction ≥90% in comparison with the relaxed state following intracoronary nitroglycerine administration given to relieve the spasm, associated with the reproduction of the patient's anginal symptoms and ischemic ECG shifts. Microvascular spasm will be diagnosed when typical ischemic ST-segment changes and angina develop in the absence of epicardial coronary constriction (< 90% diameter reduction). Patients who will not experience angina, spasm, or ST-segment shifts will be considered to have a negative test response (normal coronary vasoreactivity). Similarly, patients who will experience ischemic ECG shifts without angina or patients with chest pain without ischemic ECG shifts will be considered to have a negative test response.

Statistical analysis Statistical analysis will be performed using statistical software package Statistic for Data Analysis Stata 17 (64 bit; StataCorp, College Station, TX) and GraphPad Prism version 8.0.2 (GraphPad Software, San Diego, CA). Chi-square, Fisher's exact test and Kruskal Wallis test will be used to compare categorical variables. Continuous variables were listed as mean ± standard deviation (SD) and will be compared between groups using the Student's t-test, the Mann-Whitney U test, as appropriate. We will perform a 2-tailed analysis and consider a p-value ≤0.05 to be significant. With respect to the primary endpoint, all events occurring from randomization to the study end date will be counted. The number and rate of patients experiencing a primary endpoint will also be summarized. The proportion of patients remaining event-free over time will be displayed in the form of survival curves using the Kaplan-Meier method and analyzed using the log-rank test and the Gehan-Breslow-Wilcoxon test. With respect to secondary endpoints, a Cox proportional hazards model will be used, and estimates of the hazard ratios and their confidence intervals will be provided. In general, missing values will remain as missing, i.e., no attempt will be made to impute missing values and only observed values will be used in data analyses. An interim analysis will be performed on the primary endpoint when 50% of patients will have been randomized and completed the 6 months follow-up. The interim analysis will be performed by an independent statistician, blinded for the treatment allocation.

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Acquaviva Delle Fonti, Italy
        • Not yet recruiting
        • Ospedale Generale Regionale F. Miulli
      • Alessandria, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo
      • Arezzo, Italy
        • Not yet recruiting
        • Ospedale San Donato
      • Bergamo, Italy
        • Not yet recruiting
        • Asst Papa Giovanni XXIII
      • Biella, Italy
        • Not yet recruiting
        • Ospedale degli Infermi di Biella
      • Bologna, Italy
        • Not yet recruiting
        • Policlinico S. Orsola IRCCS Azienda Ospedaliero Universitaria
      • Caserta, Italy
        • Not yet recruiting
        • Azienda Ospedaliera di Rilievo Nazionale Sant'Anna e San Sebastiano
      • Cotignola, Italy
        • Not yet recruiting
        • Villa Maria Cecilia Hospital
      • Ferrara, Italy
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Di Ferrara
      • Firenze, Italy
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Careggi
      • Genova, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Policlinico San Martino
      • Grosseto, Italy
        • Not yet recruiting
        • Ospedale della Misericordia
      • Milano, Italy
        • Not yet recruiting
        • Centro Cardiologico Monzino IRCCS
      • Milano, Italy
        • Not yet recruiting
        • IRCCS Ospedale Galeazzi
      • Monza, Italy
        • Not yet recruiting
        • Fondazione IRCCS San Gerardo dei Tintori
      • Novara, Italy, 28100
        • Recruiting
        • AOU Maggiore della Carità
        • Contact:
        • Principal Investigator:
          • Domenico D'Amario, Prof
        • Principal Investigator:
          • Giuseppe Patti, Prof
      • Parma, Italy
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria di Parma
      • Perugia, Italy
        • Not yet recruiting
        • Azienda Ospedaliera di Perugia
      • Pisa, Italy
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Pisana
      • Pistoia, Italy
        • Not yet recruiting
        • Ospedale San Jacopo
      • Rivoli, Italy
        • Not yet recruiting
        • Ospedali Riuniti di Rivoli
      • Roma, Italy
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Roma, Italy
        • Not yet recruiting
        • Azienda Ospedaliera San Camillo-Forlanini
      • Roma, Italy
        • Not yet recruiting
        • Ospedale Santo Spirito
      • Roma, Italy
        • Not yet recruiting
        • Aurelia Hospital
      • Roma, Italy
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Sant'Andrea
      • Roma, Italy
        • Not yet recruiting
        • Ospedale Sandro Pertini
      • Roma, Italy
        • Not yet recruiting
        • Policlinico Universitario Tor Vergata Fondazione PTV
      • Sassari, Italy
        • Not yet recruiting
        • Ospedale Civile Santissima Annunziata
      • Siracusa, Italy
        • Not yet recruiting
        • Azienda Sanitaria Provinciale di Siracusa
      • Torino, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Ordine Mauriziano
      • Torino, Italy
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Città Della Salute E Scienza
      • Vercelli, Italy
        • Not yet recruiting
        • Presidio Ospedaliero Sant'Andrea
      • Verona, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Integrata, Ospedale Borgo Trento

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Ability to give informed consent to the study.
  2. Age ≥ 18 years and ≤ 75 years.
  3. Diagnosis of MB during index coronary angiography*.
  4. Symptoms or signs of inducible ischemia (if signs, these should involve the territory of the index vessel).

Angiographic definition of MB *

Myocardial bridge is a congenital anomaly characterized by an intramural course of an epicardial coronary segment. This anatomical arrangement causes the artery to be squeezed during systole, with a relaxation in diastole. In this study, MB is defined as a visual ≥ 50% reduction in the minimal luminal diameter during systole and a complete or partial relaxation in diastole ("milking effect").

The use of intracoronary vasodilators (i.e., nitrates) can increase the systolic narrowing of the vessel, through a reflex rise of the adrenergic drive, and consequently the angiographic sensitivity in detecting MB.

Exclusion Criteria:

  1. Moderate to severe CAD (≥ 50% stenosis in any vessel, including chronic total occlusion) at the time of enrolment/randomization.
  2. Previous CABG involving the index vessel.
  3. Severe valvular heart disease.
  4. Left ventricular systolic dysfunction [ejection fraction (EF) < 40%], regardless of the etiology.
  5. Clinically significant right ventricular dysfunction.
  6. Known severe renal impairment (eGFR < 30 ml/min/1.73 m2).
  7. Known severe hepatic impairment, or history of cirrhosis with evidence of portal hypertension.
  8. History of malignancy of any organ system with a life expectancy < 1 year.
  9. Any previous history of ischemic stroke, intracranial haemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
  10. Pregnant or breastfeeding women.
  11. Known hypersensitivity or contraindication to any of the drugs used for coronary physiology testing (nitrates, adenosine, dobutamine, acetylcholine).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: "full-physiology approach" arm

In the "full-physiology approach" arm, patients will be, during CA, simultaneously subjected to a full interventional diagnostic procedure, including:

  • resting distal coronary pressure to aortic pressure ratio (Pd/Pa);
  • fractional flow reserve (FFR) after intravenous adenosine administration;
  • Resting Ful-Cycle Ratio (RFR);
  • coronary flow reserve (CFR) and index of microvascular resistance (IMR);
  • assessment of FFR, CFR and IMR after inotropic stimulation with dobutamine (respectively FFR-d, CFR-d and IMR-d);
  • acetylcholine (ACH) provocative test.
Diagnostic test: "full-physiology approach" arm
  • All MB patients belonging to the full-physiology arm will undergo functional assessment of the intramural artery with basal Pd/Pa, FFR (after intravenous adenosine), RFR, CFR and IMR.
  • In the presence of a negative functional assessment (Pd/Pa> 0.92, FFR> 0.80, RFR> 0.89, CFR≥ 2.0 and IMR< 25), FFR, CFR and IMR will be measured after inotropic stimulation with dobutamine (respectively FFR-d, CFR-d and IMR-d) to exalt the epicardial hemodynamic significance of MB or its impact on structural microvascular remodelling (impaired endothelium-independent vasodilatation).
  • In the absence of epicardial hemodynamic significance (FFR-d> 0.75) and structural microvascular dysfunction (CFR≥ 2.0 and IMR< 25), ACH provocative test will be performed to evaluate the presence of epicardial or microvascular spasm (impaired endothelium-dependent vasodilatation).
Other: "standard approach" arm
In the "standard approach" arm, patients will undergo only an angiographic evaluation, without any invasive intracoronary assessment.
Diagnostic test: "standard approach" arm
In the "standard approach" arm patients will undergo an angiographic evaluation of the tunnelled artery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The composite of significant angina and MACE
Time Frame: at 1-year follow-up
Composite of significant anginal burden, defined as Seattle angina questionnaire (SAQ) Summary Score ≤ 70, and MACE, defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization (any cause) and target vessel revascularization at 1 year follow-up.
at 1-year follow-up

Secondary Outcome Measures

Outcome Measure
Time Frame
Rate of patients with significant angina (SAQ Angina Summary Score ≤ 70)
Time Frame: at 1-year follow-up
at 1-year follow-up
Incidence of MACE
Time Frame: at 1-year follow-up
at 1-year follow-up
Rate of cardiac death
Time Frame: at 1-year follow-up
at 1-year follow-up
Rate of MI
Time Frame: at 1-year follow-up
at 1-year follow-up
Rate of cardiac hospitalization
Time Frame: at 1-year follow-up
at 1-year follow-up
Rate of TLR
Time Frame: at 1-year follow-up
at 1-year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero Universitaria Maggiore della Carita

Collaborators

Università degli Studi del Piemonte Orientale "Amedeo Avogadro"

Investigators

  • Study Chair: Giuseppe Patti, Prof, Università degli Studi del Piemonte Orientale "Amedeo Avogadro"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2023

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

February 15, 2024

First Submitted That Met QC Criteria

February 20, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

July 10, 2024

Last Update Submitted That Met QC Criteria

July 9, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 271.673

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myocardial Bridge

Clinical Trials on "full-physiology approach" arm

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zimbabwe

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe