Sensor-equipped Ultrathin Pressure Microcatheter Versus Pressure Wire for Physiological Measurements

Study Overview
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Brief Summary
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TruePhysio pressure microcatheter is a novel device for evaluating the functional significance of coronary stenosis, and its safety and efficacy on the measurement of hyperemic index have been validated in the previous SUPREME study (NCT03541577). This study will further evaluate the safety and efficacy of the physiological indices measured by the TruePhysio pressure microcatheter, including resting and hyperemic indices, with respect to the physiological indices measured by the Pressure Wire.

Detailed Description
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This study will evaluate the safety and efficacy of the constant-resistance ratio (cRR) measured by the TruePhysio pressure microcatheter, in both binary and hybrid strategy, with respect to its own fractional flow reserve (FFR) and the FFR or resting full-cycle ratio (RFR) by the Pressure Wire. And the safety and efficacy of the FFR measured by the TruePhysio pressure microcatheter in patients with a border range of diameter stenosis also be validated with respect to the FFR by the Pressure Wire. The diagnostic accuracy of cRR by the TruePhysio pressure microcatheter system is evaluated, using FFR measured by both systems as reference; Mean bias between the FFR values measured by TruePhysio pressure microcatheter and Pressure Wire is evaluated, using FFR measured by Pressure Wire as the reference; The diagnostic accuracy of the hybrid cRR-FFR scheme by the TruePhysio pressure microcatheter is evaluated, using its own FFR as reference; The diagnostic accuracy of the hybrid RFR-FFR scheme by the Pressure Wire system is evaluated, using its own FFR as reference. The hybrid scheme for cRR-FFR (pressure microcatheter system), or RFR-FFR (pressure wire system), is defined as following: the gray zone is defined as where the sensitivity and specificity are equal, shown as [A, B]. if cRR or RFR of the target vessel is <A, it is diagnosed as functionally positive in myocardial ischemia; if cRR or RFR of the target vessel is >B, it is diagnosed as functionally negative in myocardial ischemia; if cRR or RFR of the target vessel is between A and B (including A and B), the diagnostic criterion is superseded by that of FFR, which is: if FFR of the target vessel is > 0.80, it is diagnosed as functionally negative in myocardial ischemia; if FFR of the target vessel is ≤ 0.80, it is diagnosed as functionally positive in myocardial ischemia. A total of 487 patients are anticipated to be recruited from 11 centers in China.

Official Title
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Pressure Microcatheter for Physiological Measurements - A Prospective, Multicenter, Randomized Study

Conditions
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Coronary Artery Disease, Coronary Disease, Myocardial Ischemia

Intervention / Treatment
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* Device: Randomized physiological measurements by the two systems


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old; Having at least one 30-90% coronary artery stenosis by visual estimation under angiogram; Clinically indicated to physiological assessment. Exclusion Criteria: Unable to comprehend, or unwilling to sign the informed consent form; Contraindicated to the procedures of invasive coronary angiography or percutaneous coronary intervention; Clinically diagnosed with severe coronary artery vasospasm; Other operator-discerned facts that will make enrollment or the procedure impossible to complete.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pressure Microcatheter-First<br>Per the result of prior randomization, physiological assessment to the enrolled patient will be performed by the TruePhysio pressure microcatheter system ahead of the Pressure Wire system. | Device: Randomized physiological measurements by the two systems<br>* To measure physiological indices (FFR, cRR and RFR), either pressure microcatheter or pressure wire enters one patient's body. Whether it is the pressure microcatheter or pressure wire firstly to enter is randomized. After completion of one system's physiological assessment, the other system will follow for its physiological assessment.<br>|
| Pressure Wire-First<br>Per the result of prior randomization, physiological assessment to the enrolled patient will be performed by the Pressure Wire system ahead of the TruePhysio pressure microcatheter system, per the result of prior randomization. | Device: Randomized physiological measurements by the two systems<br>* To measure physiological indices (FFR, cRR and RFR), either pressure microcatheter or pressure wire enters one patient's body. Whether it is the pressure microcatheter or pressure wire firstly to enter is randomized. After completion of one system's physiological assessment, the other system will follow for its physiological assessment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The accuracy of cRR measured by TruePhysio pressure microcatheter in diagnosing myocardial ischemia | Using FFR measured by TruePhysio pressure microcatheter as the reference. The optimal binary cutoff for cRR is determined by using Youden's index. | Immediate upon completion of the procedure for the last enrolled patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the Receiver Operating Characteristic (ROC) curve (AUC) of cRR measured by the TruePhysio pressure microcatheter in diagnosing myocardial ischemia | Using FFR measured by TruePhysio pressure microcatheter as the reference | Immediate upon completion of the procedure for the last enrolled patient | 
| The sensitivity, specificity, positive and negative predictive values of cRR measured by TruePhysio pressure microcatheter in diagnosing myocardial ischemia | Using FFR measured by TruePhysio pressure microcatheter as the reference. The optimal binary cutoff for cRR is determined by using Youden's index. | Immediate upon completion of the procedure for the last enrolled patient | 
| The AUC of cRR measured by the TruePhysio pressure microcatheter in diagnosing myocardial ischemia | Using FFR measured by Pressure Wire as the reference | Immediate upon completion of the procedure for the last enrolled patient | 
| The overall accuracy, sensitivity, specificity, positive and negative predictive values of cRR in diagnosing myocardial ischemia | Using FFR measured by Pressure Wire as the reference. The optimal binary cutoff for cRR is determined by using Youden's index. | Immediate upon completion of the procedure for the last enrolled patient | 
| The AUC of RFR measured by the Pressure Wire in diagnosing myocardial ischemia | Using FFR measured by Pressure Wire as the reference | Immediate upon completion of the procedure for the last enrolled patient | 
| The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of RFR in diagnosing myocardial ischemia | Using FFR measured by Pressure Wire as the reference. The binary cutoff for RFR is determined by previous study as 0.89. | Immediate upon completion of the procedure for the last enrolled patient | 
| The overall accuracy, sensitivity, specificity, positive and negative predictive values of the hybrid cRR-FFR scheme, concluded by TruePhysio pressure microcatheter, in diagnosing myocardial ischemia | Using FFR measured by the TruePhysio pressure microcatheter as the reference. The gray zone is defined as where the false positive and negative ratios are equal. | Immediate upon completion of the procedure for the last enrolled patient | 
| The proportion of the subcohort, whose cRR value is in the gray zone of the hybrid cRR-FFR scheme, to the entire cohort | Using FFR measured by the TruePhysio pressure microcatheter as the reference. Each enrolled patient only has one vessel to be physiologically assessed. | Immediate upon completion of the procedure for the last enrolled patient | 
| When the cRR value is out of the gray zone of the hybrid cRR-FFR scheme, the cRR-FFR hybrid scheme's accuracy in diagnosing myocardial ischemia | Using FFR measured by the TruePhysio pressure microcatheter as the reference | Immediate upon completion of the procedure for the last enrolled patient | 
| The overall accuracy, sensitivity, specificity, positive and negative predictive values of the hybrid RFR-FFR scheme, concluded by Pressure Wire, in diagnosing myocardial ischemia | Using FFR measured by the Pressure Wire as the reference. The gray zone is determined by previous study as [0.86, 0.93]. | Immediate upon completion of the procedure for the last enrolled patient | 
| The proportion of the subcohort, whose RFR value is in the gray zone of the hybrid RFR-FFR scheme, to the entire cohort | Using FFR measured by the Pressure Wire as the reference. Each enrolled patient only has one vessel to be physiologically assessed. | Immediate upon completion of the procedure for the last enrolled patient | 
| When the RFR value is out of the gray zone of the hybrid RFR-FFR scheme, the RFR-FFR hybrid scheme's accuracy in diagnosing myocardial ischemia | Using FFR measured by the Pressure Wire as the reference | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Pearson correlation between the cRR and FFR measured by TruePhysio pressure microcatheter | Paired values are analyzed by Pearson correlation | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Passing-Bablok regression analysis between the cRR and FFR measured by TruePhysio pressure microcatheter | Paired values are analyzed by Passing-Bablok regression | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Pearson correlation between the RFR and FFR measured by Pressure Wire | Paired values are analyzed by Pearson correlation | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Passing-Bablok regression analysis between RFR and FFR measured by Pressure Wire | Paired values are analyzed by Passing-Bablok regression | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Passing-Bablok regression analysis between cRR measured by the TruePhysio pressure microcatheter, and RFR measured by the Pressure Wire | Paired cRR-RFR values by the two systems are analyzed in Passing-Bablok regression | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Bland-Altman analysis between cRR measured by the TruePhysio pressure microcatheter, and RFR measured by the Pressure Wire | Paired cRR-RFR values by the two systems are analyzed in Bland-Altman analysis | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Pearson's correlation between cRR measured by the TruePhysio pressure microcatheter, and RFR measured by the Pressure Wire | Paired cRR-RFR values by the two systems are analyzed in Pearson correlation | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Pearson correlation between the FFR values measured by TruePhysio pressure microcatheter and Pressure Wire | Paired FFR values by the two systems are analyzed by Pearson correlation | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Passing-Bablok regression analysis between the FFR values measured by TruePhysio pressure microcatheter and Pressure Wire | Paired FFR values by the two systems are analyzed by Passing-Bablok regression | Immediate upon completion of the procedure for the last enrolled patient | 
| Mean bias between the FFR values measured by TruePhysio pressure microcatheter and Pressure Wire as assessed by Bland-Altman analysis | Using FFR measured by Pressure Wire as the reference | Immediate upon completion of the procedure for the last enrolled patient | 
| Results of Bland-Altman analysis between the FFR values measured by TruePhysio pressure microcatheter and Pressure Wire among the patients with atrial fibrillation or in severe stenosis or with small vessels | Using FFR measured by Pressure Wire as the reference. The severe stenosis is defined as the diameter stenosis higher than 70%, while the small vessel is defined as the reference vessel diameter smaller than 2.5 mm. | Immediate upon completion of the procedure for the last enrolled patient | 
| Rate of significant drift | Drift is defined as the difference between FFR value and 1 when pressure sensor is pulled back to coronary artery ostium for verification. Significant drift occurs when the device has a drift with absolute value > 0.03; alternatively, drift is regarded as significant when the Pd/Pa at the ostium for verification is either <0.97 or >1.03. Significant drift is recorded per appearance, regardless whether the measurement is eventually successful or not. Its rate is calculated as: Times of significant drift occurred in total / Times of measuring attempted in total | Immediate upon completion of the procedure for the last enrolled patient | 
| Rate of device success | Device success is defined when a device successfully crossed the lesion and completed acquisition of valid physiological values. For any vessel, if valid cRR and FFR values by the TruePhysio pressure microcatheter are acquired, the measurement of TruePhysio pressure microcatheter is successful in the specific vessel, disregarding how many times it was attempted; For any vessel, if valid RFR and FFR values by the Pressure Wire are acquired, the measurement of Pressure Wire is successful in the specific vessel, disregarding how many times it was attempted. Rate of device success is calculated as: Vessels with device success / Total vessels | Immediate upon completion of the procedure for the last enrolled patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fractional flow reserve, constant-resistance ratio, resting full-cycle ratio