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

NCT02519608 | Completed Phase 2 DMC

• 1 other identifier: 150497
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Coronary Artery Disease; Chronic Obstructive Pulmonary Disease

Keywords

chronic obstructive pulmonary disease; stable coronary artery disease; ticagrelor; clopidogrel; endothelial function; inflammation; platelet reactivity

Outcome Measures

Primary Outcomes (1)

• apoptosis rate in HUVEC

  reduction of the rate of apoptosis in human umbilical vein endothelial cells (HUVEC) incubated with serum from patients enrolled in the study.

  1 month

Secondary Outcomes (7)

• on-treatment platelet reactivity

  1 month

• NO intracellular levels

  1 month

• ROS production

  1 month

• inflammation markers levels

  1 month

• ischemic adverse events

  1 month

Other Outcomes (4)

• apoptosis rate in HUVEC

  time between LD and end of PCI, expected average of 5 hours

• on-treatment platelet reactivity

  time between LD and end of PCI, expected average of 5 hours

• NO intracellular levels

  time between LD and end of PCI, expected average of 5 hours

Study Arms (2)

Aspirin 100 mg + Clopidogrel 75 mg

ACTIVE COMPARATOR

dual antiplatelet therapy as suggested by guidelines with aspirin 100 mg and clopidogrel 75 mg daily

Drug: Aspirin 100 mg; Drug: Clopidogrel

Aspirin 100 mg + Ticagrelor 90 mg x2

EXPERIMENTAL

dual antiplatelet therapy with aspirin 100 mg and ticagrelor 90 mg x 2 daily

Drug: Aspirin 100 mg; Drug: Ticagrelor

Interventions

Aspirin 100 mg DRUG

Patients with COPD and SCAD undergoing PCI and stent implantation will receive aspirin

Also known as: baseline background treatment

Aspirin 100 mg + Clopidogrel 75 mg; Aspirin 100 mg + Ticagrelor 90 mg x2

Ticagrelor DRUG

Patients with COPD and SCAD undergoing PCI and stent implantation will receive according randomization aspirin + ticagrelor (loading dose 180 mg + maintenance 90 mg x2)

Also known as: new hypothesis group

Aspirin 100 mg + Ticagrelor 90 mg x2

Clopidogrel DRUG

Patients with COPD and SCAD undergoing PCI and stent implantation will receive according randomization aspirin + clopidogrel (loading dose 600 mg + maintenance 75 mg)

Also known as: gold standard P2Y12 treatment

Aspirin 100 mg + Clopidogrel 75 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Age ≥18 years;
• Ability to provide informed written consent and to participate in the 6-months follow-up period;
• Diagnosis of SCAD requiring coronary artery angiography
• COPD diagnosis confirmed by spirometry in stable phase and after medical treatment from at least 3 months.
• Patients hospitalized with diagnosis of acute coronary syndrome
• Previous chronic use of P2Y12 inhibitors
• Known intolerance to aspirin and/or P2Y12 inhibitors
• Absence of significant variation in guideline driven medical treatment in the last 15 days
• History of intracranial haemorrhage
• Known intake of a strong CYP3A4 inhibitor (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir),
• Known pregnancy, breast-feeding, or intend to become pregnant during the study period
• Planned surgery, including CABG as a staged procedure (hybrid) within 6 months;
• Known moderate to severe hepatic impairment (alanine-aminotransferase ≥ 3 x ULN);
• Need for chronic oral anti-coagulation therapy;
• Active major bleeding or major surgery within the last 30 days;

Sponsors & Collaborators

• University Hospital of Ferrara: lead

Study Sites (1)

University Hospital of Ferrara

Cona, Ferrara, 44124, Italy

Location

Related Publications (1)

• Campo G, Vieceli Dalla Sega F, Pavasini R, Aquila G, Gallo F, Fortini F, Tonet E, Cimaglia P, Del Franco A, Pestelli G, Pecoraro A, Contoli M, Balla C, Biscaglia S, Rizzo P, Ferrari R. Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease. Thromb Haemost. 2017 Mar 23;117(6):1208-1216. doi: 10.1160/TH16-12-0973. Epub 2017 Mar 23.

  PMID: 28331925 RESULT

MeSH Terms

Conditions

Coronary Artery Disease; Pulmonary Disease, Chronic Obstructive; Inflammation

Interventions

Aspirin; Ticagrelor; Clopidogrel

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor and Interventional Cardiologist

Study Record Dates

• First Submitted: July 31, 2015
• First Posted: August 11, 2015
• Study Start: September 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: January 1, 2017
• Last Updated: May 2, 2018

Record last verified: 2018-05

Locations

IT (1)