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

Fundacion Investigacion Interhospitalaria Cardiovascular

Status and phase: Unknown; Phase 4

Conditions: Diabetes Mellitus, Type 2

Treatments: Procedure: Diagnostic; Procedure: PCI; Drug: Randomization

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02698618

ESR-15-10793

2015-003621-33 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject with Diabetes Mellitus (DM) Type II
• 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

• Prior myocardial infarction in the territory of the target vessel
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Ticagrelor

Experimental group

Description:

A loading dose of Ticagrelor 180mg followed by a dose of 90mg b.i.d. (during 48 hours)

Treatment:

Procedure: Diagnostic

Procedure: PCI

Drug: Randomization

Clopidogrel

Active Comparator group

Description:

A loading dose of Clopidogrel 600mg followed by a daily dose (during at least 48 hours) of 75mg

Treatment:

Procedure: Diagnostic

Procedure: PCI

Drug: Randomization