ENHANCE: Antiplatelet Therapies in Patients With Depression and Coronary Disease

Sponsor

Centro Cardiologico Monzino (Other)

Overall Status

Recruiting

CT.gov ID

NCT05821062

Collaborator

IRCCS National Neurological Institute "C. Mondino" Foundation (Other)

400

Enrollment

Locations

21.6

Anticipated Duration (Months)

200

Patients Per Site

9.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Depression after an acute coronary syndrome (ACS) but also at any time after CAD diagnosis, is highly associated with death, and it predicts mortality more than any other risk factor, comorbidity or follow-up events, suggesting that the standard medical therapy may not be sufficient to prevent the poor prognosis in these patients.

This study aims to assess whether depression might affect the response to dual antiplatelet therapy (DAPT) as recommended in coronary artery disease (CAD) patients.

Specific aims:

to evaluate whether depression affects the antithrombotic response during Aspirin (ASA) plus clopidogrel (CLP) therapy in CAD patients.
to assess the antithrombotic effects of ASA plus ticagrelor or prasugrel (TCG/PSG) therapy in CAD patients with depression by evaluating pro-thrombotic phenotype in CAD patients with and without depression during ASA+TCG/PSG.
to assess whether there is or not the reactivation of pro-thrombotic profile after cessation of dual antiplatelet therapy in CAD patients with or without depression in single antiplatelet therapy after TCG/PSG cessation.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Depression	Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy Other: standard ASA therapy

Detailed Description

This study is a multicentre, prospective, observational, case-control, and cross-sectional study. It is planned to enrol 400 patients/subjects (300 patients at Centro Cardiologico Monzino and 100 subjects at IRCCS National Neurological Institute "C. Mondino" Foundation).

Pharmacological treatments in progress will be recorded, administration of Beck Depression Inventory-II (BDI-II), and a fasting blood venous sample (from ante-cubital vein) will be carried out for the haematochemical analyses and for research samples. First morning-urine will be collected for oxidative stress evaluation.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Effect of Antiplatelet Therapies in Patients With Depression and Coronary Disease

Actual Study Start Date :

Apr 14, 2022

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Group 1a CAD patients with depression on standard ASA+CLP therapy.	Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy ASA100mg + CLP 75mg daily
Group 1b CAD Patients without depression on standard ASA+CLP therapy.	Other: standard Aspirin (ASA) + clopidogrel (CLP) therapy ASA100mg + CLP 75mg daily
Group 2a CAD patients with depression on standard ASA+TCG/PSG therapy.	Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy ASA 100 mg + TCG 90mg/b.i.d or PSG10mg daily
Group 2b CAD patients without depression on standard ASA+TCG/PSG therapy.	Other: standard Aspirin (ASA) + Ticagrelor (TCG) or Prasugrel (PSG) therapy ASA 100 mg + TCG 90mg/b.i.d or PSG10mg daily
Group 3a CAD patients with depression on standard ASA treatment alone at least 1 month after TCG/PSG cessation.	Other: standard ASA therapy ASA 100 mg daily
Group 3b CAD patients without depression on standard ASA treatment alone at least 1 month after TCG/PSG cessation.	Other: standard ASA therapy ASA 100 mg daily
Group 1c Subjects with depression without CAD (DS) are enrolled are enrolled as a comparison group.
Group 1d Healthy control subjects (HC), subjects without depression and without CAD are enrolled as a comparison group.

Outcome Measures

Primary Outcome Measures

Verify whether depression affects the platelet response during ASA plus CLP therapy in CAD patients [3 years]
Measuring platelet activity markers
Verify whether depression affects the coagulation during ASA plus CLP therapy in CAD patients [3 years]
Measuring all the parameters of clot formation and lysis collected by thromboelastography analyses
Verify whether depression affects oxidative stress during ASA plus CLP therapy in CAD patients [3 years]
Measuring lipid peroxidation
Assess the effects of ASA plus TCG/PSG therapy on platelet response in CAD patients with depression [3 years]
Measuring platelet activity markers
Assess the effects of ASA plus TCG/PSG therapy on coagulation in CAD patients with depression [3 years]
Measuring all the parameters of clot formation and lysis collected by thromboelastography analyses
Assess the effects of ASA plus TCG/PSG therapy on oxidative stress in CAD patients with depression [3 years]
Measuring lipid peroxidation
Assess whether there is or not the activation of platelet response after cessation of dual antiplatelet therapy in CAD patients with depression [3 years]
Measuring platelet activity markers
Assess whether there is or not the activation of coagulation after cessation of dual antiplatelet therapy in CAD patients with depression [3 years]
Measuring all the parameters of clot formation and lysis collected by thromboelastography analyses
Assess whether there is or not the activation of oxidative stress after cessation of dual antiplatelet therapy in CAD patients with depression [3 years]
Measuring lipid peroxidation

Secondary Outcome Measures

CLP metabolism in patients with depression and CAD [3 years]
Measuring the CLP active metabolite
Epigenetic modification in patients with depression and CAD [3 years]
Through miRNAs analysis
DNA methylation in patients with depression and CAD [3 years]
Measuring DNA methylation levels of two 5'-C-phosphate-G-3' (CpG) dinucleotides on P2Y12
Impact of depression on oxidative stress in patients without CAD [3 years]
Measuring platelet activity markers
Effect of depression on oxidative stress in patients without CAD [3 years]
Measuring lipid peroxidation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Centro Cardiologico Monzino: Patients/subjects of both sexes, aged between 18 and 85 years with or without depression, with CAD:

Group 1: CAD patients in ASA+CLP (100mg+75mg/daily) therapy with the absence of acute coronary symptoms for at least 5 months.
Group 2: CAD patients in ASA+TCG/PSG (TCG:90mg/b.i.d or PSG:10mg/daily) therapy, at least 6 months after ACS.
Group 3: CAD patients during ASA treatment alone at least 1 month after TCG/PSG cessation.

IRCCS National Neurological Institute "C. Mondino" Foundation:

Group 1: Patients/subjects of both sexes, aged between 18 and 85 years with or without depression, without CAD.

Exclusion Criteria:

severe chronic heart failure (NYHA class III/IV)
severe concomitant valvular disease
infectious pathologies
autoimmune diseases
haematological diseases
serious kidney or liver failure
positive anamnesis for current or previous neoplasia in the 5 years prior to enrolment
positive anamnesis for major traumas and/or surgery in the 6 months prior to enrolment
taking immunosuppressive drugs
taking of anti-inflammatory drugs
taking of antidepressant drugs
presence of dementia and psychiatric disorders other than depression
Coronavirus disease-19 (COVID-19) swab positive