ComparisoN of ticAgrelor vs. Clopidogrel in endoTHeliAl Function of COPD patieNts

• Status: Completed
• Trial end date: 2017-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an investigator-initiated, prospective, single-centre, randomised, phase II, open-label study, testing the superiority of ticagrelor, as compared to clopidogrel, in modulating on-P2Y12 treatment platelet reactivity, endothelial dysfunction and inflammation in chronic obstructive pulmonary disease (COPD) patients receiving scheduled percutaneous coronary intervention (PCI) for stable coronary artery disease. Subjects that meet the inclusion criteria and have provided informed consent will be randomly assigned in a 1:1 fashion to one of the two dual antiplatelet therapy (DAPT) regimen: aspirin + clopidogrel (standard of care) vs. aspirin + ticagrelor (experimental arm).

DAPT with aspirin and clopidogrel for at least 6 months (preferably 12 months) is the current gold-standard for patients receiving PCI and drug eluting stent implantation for SCAD. No data supports a different strategy and/or approach in COPD patients undergoing PCI. Ticagrelor, a new P2Y12 inhibitor, showed a significantly higher platelet inhibition as compared to clopidogrel. Recently, ticagrelor administration has been associated with a positive effect on endothelial function and a modulation of proinflammatory signalling. These actions are mediated by a significant influence of adenosine uptake. Higher platelet reactivity, chronic inflammatory response, heightened endothelial dysfunction characterized COPD patients with concomitant coronary artery disease (CAD). The investigators speculated that COPD patients undergoing PCI for stable CAD (SCAD) had a risk profile similar to that of acute coronary syndromes (ACS) patients. Accordingly, COPD patients undergoing PCI for SCAD may obtain a stronger benefit by ticagrelor as compared to clopidogrel. The aim of this study is to evaluate whether ticagrelor, is superior to clopidogrel, in reducing endothelial dysfunction , platelet reactivity (PR) and inflammation profile of patients with stable CAD and COPD. Ticagrelor will be administered according PLATO trial and international guidelines (180 mg as loading dose, 90 mg x 2 daily as maintenance dose). As suggested by international guidelines, the control group will be patients with current gold standard treatment for SCAD treated with PCI (aspirin + clopidogrel 75 mg daily). The evaluation of endothelial dysfunction, PR and inflammation profile will be repeated after 30 days and will be compared to baseline values.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital of Ferrara
• Treatments: Aspirin; Clopidogrel; Ticagrelor; Ticlopidine

Criteria

Type of Patients Subjects either male or female eligible for PCI and undergoing drug eluting stent implantation who have meet all inclusion criteria and did not meet any of the exclusion criteria.

Inclusion Criteria:

For inclusion in the study subjects should fulfill the following criteria:

1. Age ≥18 years;

2. Ability to provide informed written consent and to participate in the 6-months follow-up period;

3. Diagnosis of SCAD requiring coronary artery angiography

4. COPD diagnosis confirmed by spirometry in stable phase and after medical treatment from at least 3 months.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Patients hospitalized with diagnosis of acute coronary syndrome

2. Previous chronic use of P2Y12 inhibitors

3. Known intolerance to aspirin and/or P2Y12 inhibitors

4. Absence of significant variation in guideline driven medical treatment in the last 15 days

5. History of intracranial haemorrhage

6. Known intake of a strong CYP3A4 inhibitor (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir),

7. Known pregnancy, breast-feeding, or intend to become pregnant during the study period

8. Planned surgery, including CABG as a staged procedure (hybrid) within 6 months;

9. Known moderate to severe hepatic impairment (alanine-aminotransferase ≥ 3 x ULN);

10. Need for chronic oral anti-coagulation therapy;

11. Active major bleeding or major surgery within the last 30 days;

12. Known stroke (any type) within the last 30 days;

13. Currently participating in another trial before reaching primary endpoint;

14. Thrombocytopenia;

15. Increased risk of bradycardia;

16. Known other inflammatory chronic disorders;

17. Known or suspected malignancy

18. Other concomitant pulmonary diseases