NCT02698618

PRotective Effect on the Coronary Microcirculation of Patients With DIabetes by Clopidogrel or Ticagrelor

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Fundacion Investigacion Interhospitalaria Cardiovascular · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether Ticagrelor has a protective effect on microcirculation during percutaneous coronary interventions in patients with Diabetes mellitus type II or in a pre-diabetic status.

Detailed description

Introduction: 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

• Diabetes Mellitus, Type 2

Interventions

Type	Name	Description
PROCEDURE	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.
DRUG	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.
PROCEDURE	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).

Timeline

• Start date: 2016-03-01
• Primary completion: 2017-03-01
• Completion: 2017-03-01
• First posted: 2016-03-04
• Last updated: 2016-03-04

Locations

3 sites across 1 country: Spain