Ignite Creation Date:
2024-05-06 @ 6:23 PM
Last Modification Date:
2024-10-26 @ 2:47 PM
Study NCT ID:
NCT05643586
Status:
COMPLETED
Last Update Posted:
2022-12-08
First Post:
2022-11-30
Brief Title:
Effects of Ticagrelor Versus Prasugrel on Coronary Microcirculation in Patients Undergoing Elective Percutaneous Coronary Intervention Results of the PROtecting MICROcirculation During Coronary Angioplasty PROMICRO-3 Randomised Study
Sponsor:
Germano Di Sciascio
Organization:
Campus Bio-Medico University
Study Overview
Official Title:
Effects of Ticagrelor Versus Prasugrel on Coronary Microcirculation in Patients Undergoing Elective Percutaneous Coronary Intervention Results of the PROtecting MICROcirculation During Coronary Angioplasty PROMICRO-3 Randomised Study
Status:
COMPLETED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PROMICRO-3
Brief Summary:
Besides being at least as effective as prasugrel in inhibiting platelet aggregation ticagrelor has been shown to have additional properties potentially affecting coronary microcirculation We sought to compare the effects of ticagrelor and prasugrel on absolute coronary blood flow Q and microvascular resistance R in patients with stable coronary artery disease CAD undergoing elective percutaneous coronary intervention PCI
The PROMICRO-3 study shows that in patients with stable CAD undergoing PCI pre-treatment with a loading dose of ticagrelor compared with prasugrel improves post-procedural coronary flow and microvascular function and seems to reduce the related myocardial injury
The PROMICRO-3 study shows that in patients with stable CAD undergoing PCI pre-treatment with a loading dose of ticagrelor compared with prasugrel improves post-procedural coronary flow and microvascular function and seems to reduce the related myocardial injury
Detailed Description:
Patient population We enrolled patients naïve to platelet P2Y12 receptor inhibitors with stable CAD referred to elective percutaneous coronary intervention PCI of an isolated functionally significant as confirmed by a fractional flow reserve FFR 080 stenosis located in the proximal two-thirds of a major coronary artery
Study protocol Patients were randomly assigned to receive loading doses of either ticagrelor 180 mg or prasugrel 60 mg at least 12 hours before intervention Assignment to one of the two treatments was determined by a computer-based randomization system and randomization assignment for each patient was kept in a sealed envelope At least 12 hours before PCI average 13811 a study nurse not involved in the procedure was responsible of opening the sealed envelope and administering study drugs according to treatment allocation Both the patient and the catheterization laboratory team operator and scrubbed nurse were blinded to the assigned treatment The PCI procedures were performed by standard technique In all cases balloon pre-dilatation was performed before stent implantation
Adjunctive medications All patients were administered a 500-mg loading dose of aspirin the day before the procedure In the catheterization laboratory all patients received a weight-adjusted intravenous heparin bolus 100 IUkg in order to maintain activated clotting time between 250 and 300 seconds Patients randomized to the prasugrel group received clopidogrel 75 mg once daily as of the day after the PCI whereas patients randomized to the ticagrelor group received a 600-mg loading dose the day after PCI and a 75-mg maintenance dose as of the next day8
Coronary physiology indexes Coronary physiology indexes were measured in each patient before and after PCI Briefly an intracoronary pressuretemperature sensor-tipped guide wire PressureWire X Abbott IL was advanced through the guiding catheter in the distal segment of the target coronary artery A dedicated monorail catheter RayFlow Hexacath Paris France allowing the infusion of saline through 4 outer side holes and the measurement of temperature by the guidewire through 2 inner side holes was then advanced over the guidewire The tip of the infusion catheter was placed in the first centimeter of the coronary artery and the catheter was connected to an infusion pump Medrad Stellant Medrad Inc Warrendale PA and saline at room temperature infused at a pre-specified flow rate Qi 20 mLmin for the left anterior descending LAD and left circumflex artery LCx and 15 mLmin for the right coronary artery RCA resulting in a hyperaemic state similar to that produced by adenosine The temperature of the salineblood mixture T and the distal coronary pressure Pd were measured after achieving a steady state Aortic pressure Pa was measured through the guiding catheter Fractional flow reserve FFR was calculated as PdPa during hyperaemia The temperature of the infused saline Ti was measured after pulling the temperature sensor of the guidewire back into the infusion catheter Pressure tracings and temperatures were simultaneously analysed by a dedicated console equipped with software that automatically calculates physiology indexes Coroventis Coroflow Uppsala Sweden Q was calculated as 108 x TiT x Qi and expressed in mlmin Following the Ohms law R was calculated as PdQ and expressed as mm HgLmin or Wood units
Platelet function analysis Platelet reactivity was measured before study drug assignment and at the time of PCI using the VerifyNow P2Y12 assay Accumetrics San Diego California The VerifyNow P2Y12 assay is a validated optical turbidimetric point-of-care assay specifically assessing the effects of P2Y12 receptor inhibitors12 the results are reported as P2Y12 reaction units PRU and the lower the PRU value the higher the platelet aggregation inhibition
Peri-procedural myocardial injury High sensitivity Troponin I hs-TnI Roche Diagnostics Mannheim Germany was determined in blood samples taken before 8 and 24 hours after the intervention Peak post-PCI hs-TnI levels were considered for the analysis
Statistical analysis At the time the study was conceived no published data were available on this topic However an estimate of Q values was assumed from preliminary data collected at our Institution10 Expecting a 20 reduction in post-PCI R with ticagrelor compared with prasugrel 32075 vs 40085 mmHglmin a total of at least 23 patients per group were needed to achieve 90 power at a 2-sided alpha of 005 to detect the anticipated difference Therefore we aimed at enrolling a total of 50 patients 25 per group Continuous variables are expressed as mean SD or as median 25th 75th percentile as appropriate Categorical variables are reported as frequencies and percentages Normal distribution was tested with the Shapiro-Wilk W test Comparisons between continuous variables were performed using the Student t test or Mann-Whitney test These tests were corrected for repeated measures where appropriate Repeated measures 2-way analysis of variance ANOVA was used to assess the effect interaction between treatment and time on continuous variables Comparisons between categorical variables were evaluated using the Fisher exact test or the Pearson chi-square test as appropriate Correlations between continuous variables were assessed using the Spearman correlation test Statistical analysis was performed using STATAIC 14 STATA Corp College Station Texas and p values 005 two tailed were considered significant
Study protocol Patients were randomly assigned to receive loading doses of either ticagrelor 180 mg or prasugrel 60 mg at least 12 hours before intervention Assignment to one of the two treatments was determined by a computer-based randomization system and randomization assignment for each patient was kept in a sealed envelope At least 12 hours before PCI average 13811 a study nurse not involved in the procedure was responsible of opening the sealed envelope and administering study drugs according to treatment allocation Both the patient and the catheterization laboratory team operator and scrubbed nurse were blinded to the assigned treatment The PCI procedures were performed by standard technique In all cases balloon pre-dilatation was performed before stent implantation
Adjunctive medications All patients were administered a 500-mg loading dose of aspirin the day before the procedure In the catheterization laboratory all patients received a weight-adjusted intravenous heparin bolus 100 IUkg in order to maintain activated clotting time between 250 and 300 seconds Patients randomized to the prasugrel group received clopidogrel 75 mg once daily as of the day after the PCI whereas patients randomized to the ticagrelor group received a 600-mg loading dose the day after PCI and a 75-mg maintenance dose as of the next day8
Coronary physiology indexes Coronary physiology indexes were measured in each patient before and after PCI Briefly an intracoronary pressuretemperature sensor-tipped guide wire PressureWire X Abbott IL was advanced through the guiding catheter in the distal segment of the target coronary artery A dedicated monorail catheter RayFlow Hexacath Paris France allowing the infusion of saline through 4 outer side holes and the measurement of temperature by the guidewire through 2 inner side holes was then advanced over the guidewire The tip of the infusion catheter was placed in the first centimeter of the coronary artery and the catheter was connected to an infusion pump Medrad Stellant Medrad Inc Warrendale PA and saline at room temperature infused at a pre-specified flow rate Qi 20 mLmin for the left anterior descending LAD and left circumflex artery LCx and 15 mLmin for the right coronary artery RCA resulting in a hyperaemic state similar to that produced by adenosine The temperature of the salineblood mixture T and the distal coronary pressure Pd were measured after achieving a steady state Aortic pressure Pa was measured through the guiding catheter Fractional flow reserve FFR was calculated as PdPa during hyperaemia The temperature of the infused saline Ti was measured after pulling the temperature sensor of the guidewire back into the infusion catheter Pressure tracings and temperatures were simultaneously analysed by a dedicated console equipped with software that automatically calculates physiology indexes Coroventis Coroflow Uppsala Sweden Q was calculated as 108 x TiT x Qi and expressed in mlmin Following the Ohms law R was calculated as PdQ and expressed as mm HgLmin or Wood units
Platelet function analysis Platelet reactivity was measured before study drug assignment and at the time of PCI using the VerifyNow P2Y12 assay Accumetrics San Diego California The VerifyNow P2Y12 assay is a validated optical turbidimetric point-of-care assay specifically assessing the effects of P2Y12 receptor inhibitors12 the results are reported as P2Y12 reaction units PRU and the lower the PRU value the higher the platelet aggregation inhibition
Peri-procedural myocardial injury High sensitivity Troponin I hs-TnI Roche Diagnostics Mannheim Germany was determined in blood samples taken before 8 and 24 hours after the intervention Peak post-PCI hs-TnI levels were considered for the analysis
Statistical analysis At the time the study was conceived no published data were available on this topic However an estimate of Q values was assumed from preliminary data collected at our Institution10 Expecting a 20 reduction in post-PCI R with ticagrelor compared with prasugrel 32075 vs 40085 mmHglmin a total of at least 23 patients per group were needed to achieve 90 power at a 2-sided alpha of 005 to detect the anticipated difference Therefore we aimed at enrolling a total of 50 patients 25 per group Continuous variables are expressed as mean SD or as median 25th 75th percentile as appropriate Categorical variables are reported as frequencies and percentages Normal distribution was tested with the Shapiro-Wilk W test Comparisons between continuous variables were performed using the Student t test or Mann-Whitney test These tests were corrected for repeated measures where appropriate Repeated measures 2-way analysis of variance ANOVA was used to assess the effect interaction between treatment and time on continuous variables Comparisons between categorical variables were evaluated using the Fisher exact test or the Pearson chi-square test as appropriate Correlations between continuous variables were assessed using the Spearman correlation test Statistical analysis was performed using STATAIC 14 STATA Corp College Station Texas and p values 005 two tailed were considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None