PRotective Effect on the Coronary Microcirculation of Patients With DIabetes by Clopidogrel or Ticagrelor
NCT ID: NCT02698618
Last Updated: 2016-03-04
Study Results
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Basic Information
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UNKNOWN
PHASE4
50 participants
INTERVENTIONAL
2016-03-31
2017-03-31
Brief Summary
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Detailed Description
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Patients with Diabetes Mellitus (DM) Type 2 still consistently perform worse than their non-diabetic counterparts especially in the setting of Percutaneous Coronary Intervention (PCI). The abnormal coronary microcirculation along with the higher risk of distal embolization of particles released from the PCI target lesion constitutes the main cause of peri-procedural microcirculatory damage.
New antiplatelet agents, in particular Ticagrelor, might also play a protective role on microcirculation. Ticagrelor inhibits cellular uptake of adenosine, increasing the circulating levels of adenosine through the inhibition of its physiological clearance. Adenosine may protect the myocardium from both ischemic, and reperfusion injury via its potent vasodilatory effects and possibly by anti-inflammatory and antiplatelet properties.
Additionally previous research have identified a more profound effect of adenosine on microcirculatory resistance associated to obesity and diabetes and a higher myocardial protective effect of Ticagrelor during PCI might be expected in this high risk subgroup of patients.
The purpose of PRotective Effect on the Coronary Microcirculation of Patients With DIabetes by Clopidogrel or Ticagrelor (PREDICT) trial was designed to investigate the protective effect of Ticagrelor on microcirculation during PCI in stable diabetic patient
Rationale:
1. Coronary plaques at high risk for distal embolization during PCI, like the one with thin-cap fibroatheroma (TCFA), are more prevalent in patient with DM. Thus, this population is at high risk to develop myocardial injury and microcirculation impairment subsequent to PCI.
2. By blocking the Adenosine transporter (ENT) 1 nucleoside cell membrane transporter, Ticagrelor inhibits cellular uptake of adenosine, increasing the circulating levels of adenosine through the inhibition of its physiological clearance. Adenosine may protect the myocardium from both ischemic, and reperfusion injury via its potent vasodilatory effects and possibly by anti-inflammatory and antiplatelet properties. This translates into an adenosine-mediated vasodilatory effect of ticagrelor that takes place soon after loading dose.
3. Previous research from our group have identified a more profound effect of adenosine on microcirculatory resistance associated to obesity and diabetes and a higher myocardial protective effect of Ticagrelor during PCI might be expected in this high risk subgroup of patients. (enhanced microcirculatory response to raised adenosine levels).
Giving these premises in diabetics or pre-diabetics patients, Ticagrelor treatment pre-PCI might improve microcirculatory parameters (lower resistance) compared with clopidogrel (secondary hypothesis). Ticagrelor might be superior to clopidogrel in providing microcirculatory protection during PCI procedures in the same subgroup of patients (primary hypothesis).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Ticagrelor
A loading dose of Ticagrelor 180mg followed by a dose of 90mg b.i.d. (during 48 hours)
Diagnostic
Pre-PCI and treatment:
1. At hospital admission: all consecutive patients referred for coronary angiography in stable ischemic heart disease will undergo a complete physical examination, Electrocardiogram (ECG) and laboratory blood testing including cardiac troponin and kinase mioband. Subjects will be investigated to confirm or diagnose existing diabetic or pre-diabetic status.
2. At the time of diagnostic catheterization After informed consent, diabetic or pre-diabetic patients with at least one stenosis with a Fractional Flow Reserve value (FFR) ≤ 0.80 fulfilling all the inclusion/exclusion criteria will be included in the trial.At the same time, a multimodal physiology assessment, including Coronary Flow Reserve (CFR) and Index of Microcirculatory Resistance (IMR) will be measured.
Randomization
Randomization: patients will be randomly assigned (with 1:1 ratio) to receive either Clopidogrel or Ticagrelor before their clinically-indicated Percutaneous Coronary Intervention (PCI). Either a loading dose of Ticagrelor 180mg followed by a dose of 90mg b.i.d. (during 48 hours) or a loading dose of Clopidogrel 600mg followed by a daily dose (during at least 48 hours) of 75mg will be administered according to their randomization. Additionally the groups will be balanced according to obesity prevalence \[Body Mass Index (BMI) ≥30 kg/m2\] with the implementation of a dedicated randomization list.
PCI
1. Pre-PCI: multimodal physiological evaluation: FFR, CFR, IMR will be repeated
2. PCI: For all the patients undergoing PCI, the use of unfractioned heparin (UHF) will be allowed at the time of PCI; UFH be administered with a target on Activated Clotting Time (ACT) of 200-250 s. The PCI procedures will be performed by standard technique using only second generation Drug Eluting Stents (DES). In all cases, balloon pre-dilatation will be performed before stent implantation using a semi-compliant balloon with a diameter lower than a 75% of the distal reference diameter of the vessel to avoid confounders Post-dilation will be performed according to clinical practice although it will be not mandatory.
3. Post-PCI: After stent implantation/s, multimodal physiological evaluation will be re-performed (FFR, CFR, IMR).
Clopidogrel
A loading dose of Clopidogrel 600mg followed by a daily dose (during at least 48 hours) of 75mg
Diagnostic
Pre-PCI and treatment:
1. At hospital admission: all consecutive patients referred for coronary angiography in stable ischemic heart disease will undergo a complete physical examination, Electrocardiogram (ECG) and laboratory blood testing including cardiac troponin and kinase mioband. Subjects will be investigated to confirm or diagnose existing diabetic or pre-diabetic status.
2. At the time of diagnostic catheterization After informed consent, diabetic or pre-diabetic patients with at least one stenosis with a Fractional Flow Reserve value (FFR) ≤ 0.80 fulfilling all the inclusion/exclusion criteria will be included in the trial.At the same time, a multimodal physiology assessment, including Coronary Flow Reserve (CFR) and Index of Microcirculatory Resistance (IMR) will be measured.
Randomization
Randomization: patients will be randomly assigned (with 1:1 ratio) to receive either Clopidogrel or Ticagrelor before their clinically-indicated Percutaneous Coronary Intervention (PCI). Either a loading dose of Ticagrelor 180mg followed by a dose of 90mg b.i.d. (during 48 hours) or a loading dose of Clopidogrel 600mg followed by a daily dose (during at least 48 hours) of 75mg will be administered according to their randomization. Additionally the groups will be balanced according to obesity prevalence \[Body Mass Index (BMI) ≥30 kg/m2\] with the implementation of a dedicated randomization list.
PCI
1. Pre-PCI: multimodal physiological evaluation: FFR, CFR, IMR will be repeated
2. PCI: For all the patients undergoing PCI, the use of unfractioned heparin (UHF) will be allowed at the time of PCI; UFH be administered with a target on Activated Clotting Time (ACT) of 200-250 s. The PCI procedures will be performed by standard technique using only second generation Drug Eluting Stents (DES). In all cases, balloon pre-dilatation will be performed before stent implantation using a semi-compliant balloon with a diameter lower than a 75% of the distal reference diameter of the vessel to avoid confounders Post-dilation will be performed according to clinical practice although it will be not mandatory.
3. Post-PCI: After stent implantation/s, multimodal physiological evaluation will be re-performed (FFR, CFR, IMR).
Interventions
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Diagnostic
Pre-PCI and treatment:
1. At hospital admission: all consecutive patients referred for coronary angiography in stable ischemic heart disease will undergo a complete physical examination, Electrocardiogram (ECG) and laboratory blood testing including cardiac troponin and kinase mioband. Subjects will be investigated to confirm or diagnose existing diabetic or pre-diabetic status.
2. At the time of diagnostic catheterization After informed consent, diabetic or pre-diabetic patients with at least one stenosis with a Fractional Flow Reserve value (FFR) ≤ 0.80 fulfilling all the inclusion/exclusion criteria will be included in the trial.At the same time, a multimodal physiology assessment, including Coronary Flow Reserve (CFR) and Index of Microcirculatory Resistance (IMR) will be measured.
Randomization
Randomization: patients will be randomly assigned (with 1:1 ratio) to receive either Clopidogrel or Ticagrelor before their clinically-indicated Percutaneous Coronary Intervention (PCI). Either a loading dose of Ticagrelor 180mg followed by a dose of 90mg b.i.d. (during 48 hours) or a loading dose of Clopidogrel 600mg followed by a daily dose (during at least 48 hours) of 75mg will be administered according to their randomization. Additionally the groups will be balanced according to obesity prevalence \[Body Mass Index (BMI) ≥30 kg/m2\] with the implementation of a dedicated randomization list.
PCI
1. Pre-PCI: multimodal physiological evaluation: FFR, CFR, IMR will be repeated
2. PCI: For all the patients undergoing PCI, the use of unfractioned heparin (UHF) will be allowed at the time of PCI; UFH be administered with a target on Activated Clotting Time (ACT) of 200-250 s. The PCI procedures will be performed by standard technique using only second generation Drug Eluting Stents (DES). In all cases, balloon pre-dilatation will be performed before stent implantation using a semi-compliant balloon with a diameter lower than a 75% of the distal reference diameter of the vessel to avoid confounders Post-dilation will be performed according to clinical practice although it will be not mandatory.
3. Post-PCI: After stent implantation/s, multimodal physiological evaluation will be re-performed (FFR, CFR, IMR).
Eligibility Criteria
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Inclusion Criteria
* Subject must be older than 18 years
* Written informed consent available
* Subject with stable ischemic heart disease referred for coronary angiography
* Subject is eligible for PCI, and PCI target(s) have FFR≤0.80
Exclusion Criteria
* Akinesia or dyskinesia in subtended myocardial segments
* Severe impairment of left ventricular function (LVEF) \<35%
* PCI target is a chronic total occlusion
* Target lesion has been treated previously (restenotic lesions)
* Target vessel is a saphenous vein graft or a surgical graft has been anastomosed to target vessel
* Thrombolisis in Myocardial Infarction (TIMI) flow ≤ 1 prior to guide wire crossing
* Subject is not eligible for treatment with DES
* Bleeding disorders or chronic anticoagulant treatment
* Left main stenosis \> 50%
* Coronary surgery deemed more beneficial for the patient than PCI
* Intolerance or contraindications to anti-platelet drugs
* Contraindications for adenosine administration
* Platelet count \<75000 or \>700000/mm3
* Immunosuppressive therapy
* Pregnant or breast feeding patient
* History of intracranial haemorrhage
* Severe hepatic impairment
18 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Fundacion Investigacion Interhospitalaria Cardiovascular
OTHER
Responsible Party
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Javier Escaned
Unit head
Principal Investigators
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Javier Escaned, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital San Carlos, Madrid, Spain
Enrico Cerrato, MD
Role: PRINCIPAL_INVESTIGATOR
San Luigi Gonzaga University Hospital, Orbassano (Turin), Italy
Locations
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Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital San Carlos
Madrid, Madrid, Spain
Hospital Galdakao-Usansolo
Bilbao, Vizcaya, Spain
Countries
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Central Contacts
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Facility Contacts
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José M de la Torre, MD, PhD
Role: primary
José R Rumoroso, MD, PhD
Role: primary
References
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Cerrato E, Quiros A, Echavarria-Pinto M, Mejia-Renteria H, Aldazabal A, Ryan N, Gonzalo N, Jimenez-Quevedo P, Nombela-Franco L, Salinas P, Nunez-Gil IJ, Rumoroso JR, Fernandez-Ortiz A, Macaya C, Escaned J. PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology. Cardiovasc Diabetol. 2017 May 19;16(1):68. doi: 10.1186/s12933-017-0543-5.
Other Identifiers
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2015-003621-33
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ESR-15-10793
Identifier Type: -
Identifier Source: org_study_id
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