Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients

Stent Thrombosis Clinical Trial

— PARIS  

Official title:

Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients: An Observational Single-Arm Study (The PARIS Registry)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00998127
• Other study ID #: GCO 10-1196
• Secondary ID: 09-36709-0421-F2
• Status: Completed
• Phase: N/A
• First received: October 16, 2009
• Last updated: February 10, 2016
• Start date: June 2009
• Est. completion date: March 2013

Study information

• Verified date: February 2016
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardFrance: Institutional Ethical CommitteeGermany: Ethics CommissionItaly: Ethics CommitteeGreece: Ethics Committee
• Study type: Observational

Clinical Trial Summary

The purpose of this observational research study is to determine when and why patients discontinue, interrupt, or disrupt the regimen of anti-platelet medications prescribed following stent implantation, and to examine the relationship between specific patterns of non-adherence and patient outcomes.

Description:

Anti-platelet medicines are the cornerstone of therapy in patients who present with acute coronary syndromes, including unstable angina, non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI). Multiple clinical trials have demonstrated the efficacy of dual anti-platelet therapy (DAPT) for the prevention of thrombotic events in patients who present with unstable coronary symptoms; in particular, patients who are to receive percutaneous coronary intervention (PCI). Dual anti-platelet therapy consists of a combination of aspirin and a thienopyridine (such as clopidogrel or ticlopidine). While premature discontinuation (within the first 6 months) of such therapy is associated with an increased risk of stent thrombosis, the optimal duration of DAPT has not yet been precisely determined.

Although studies suggest an increased risk of stent thrombosis and adverse events within days after thienopyridine discontinuation, no study has collected detailed data as to the exact dates and reasons that anti-platelet agents were discontinued - thus, the true risks of premature early or even scheduled late discontinuation are unknown.

Furthermore, there are multiple modes that impact subject adherence to DAPT. These include non-compliance and cost issues.

We have determined three modes why subjects may not adhere to DAPT. These include:

• Discontinuation - These subjects have discontinued the use of DAPT (aspirin or thienopyridines) as per recommendation of their physician who has felt that the subject no longer needs this therapy.

• Interruption - These subjects have interrupted their DAPT use on a voluntary basis and under the guidance and recommendation of their physician due to the need for a surgical procedure, and will reinstitute the use of DAPT within 14 days of stopping the therapy. Interruptions must be guided by the physician/cardiologist taking care of the subject and not by other health care professionals.

• Disruption - These subjects have disrupted their DAPT use, either because of a bleeding episode (minor or major) or non-compliance. Non-compliance will include continued use of DAPT at lower dose levels than prescribed either through smaller daily doses or less frequent than daily use.

These modes have not previously been systematically collected and correlated with adverse clinical events such as stent thrombosis. Furthermore, the relation of events to subsequent disruption of DAPT has not been studied prospectively. Subjects enrolled in this registry will be followed for approximately 24 months to determine the incidence of adherence according to the above classification. All patients will have their events and DAPT use monitored during the follow-up period. The assumption is that most subjects will discontinue their therapy voluntarily (usually according to their physician's advice) and that it is only those with disrupted therapy who are at risk for major adverse cardiac events (MACE). This registry will examine the predictors of DAPT disruption based on subject's demographics and determine the relationship of bleeding versus MI in these subjects using a time-dependent covariate adjusted analysis. Finally, since there are two completely different categories within the disrupted group, (non-compliance vs. event driven disruption), we will examine these patients separately as well, as a secondary endpoint.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5031
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The subject has been informed of the nature of the study, agrees to its provisions, and has signed and been provided an "Informed Consent Form" approved by the appropriate Medical Ethics Committee (MEC) or Institutional Review Board (IRB).

• The subject must be =18 of age (or minimum age as required by local regulations) at the time of enrollment with successful stent placement in one or more lesions in native coronary arteries using an approved coronary stent.

• Diagnosis of angina pectoris as defined by Canadian Cardiovascular Society Classification (CCS I, II, III, IV), OR unstable angina pectoris (Braunwald Classification B&C, I-II-III), OR subjects with documented silent ischemia, OR acute myocardial infarction.

• The subject is willing and able to cooperate with the study procedures and required follow-ups.

Exclusion Criteria:

• Subjects with hypersensitivity or allergies to anti-platelet therapy.

• Subjects in whom anti-platelet and/or anticoagulation therapy is contraindicated.

• Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year following the index procedure.

• The subject is participating in an investigational device or drug study. Subject must have completed the follow-up phase of any previous study at least 30 days prior to enrollment in this study.

• Subject has a history of bleeding diathesis or coagulopathy.

• Subject has other medical illness (e.g., cancer, known malignancy or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that may cause non-compliance with the followups as defined by the protocol or confound the data interpretation.

• Evidence of stent thrombosis by visual angiographic assessment during the index procedure.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Medication Non-adherence
• Stent Thrombosis

Locations

Country	Name	City	State
France	Hopital Bichat	Paris
Germany	Charite - Campus Benjamin Franklin	Berlin
Greece	Onassis Cardiac Surgery Center	Athens
Italy	Careggi Hospital	Florence
Italy	San Raffaele Hospital	Milan
United States	Geisinger Medical Center Clinic	Danville	Pennsylvania
United States	LeBauer Cardiovascular Research Foundation	Greensboro	North Carolina
United States	Heart Center of Indiana	Indianapolis	Indiana
United States	Saint Luke's/ Mid-America Heart Institute	Kansas City	Missouri
United States	University of Kentucky	Lexington	Kentucky
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Washington Adventist Hospital	Takoma Park	Maryland
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Bristol-Myers Squibb, Sanofi

Countries where clinical trial is conducted

United States,  France,  Germany,  Greece,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Anti-platelet agent discontinuation/ interruption/ disruption		at 1 month	No
Primary	Incidence of Anti-platelet agent discontinuation/ interruption/ disruption		at 6 months	No
Primary	Incidence of Anti-platelet agent discontinuation/ interruption/ disruption		at 12 months	No
Primary	Incidence of Anti-platelet agent discontinuation/ interruption/ disruption		at 24 months	No
Primary	Incidence of major and minor bleeding (according to TIMI and ACUITY definitions)		at 1 month	No
Primary	Incidence of major and minor bleeding (according to TIMI and ACUITY definitions)		at 6 months	No
Primary	Incidence of major and minor bleeding (according to TIMI and ACUITY definitions)		at 12 months	No
Primary	Incidence of major and minor bleeding (according to TIMI and ACUITY definitions)		at 24 months	No
Primary	Incidence of definite and/or probable stent thrombosis (ARC definition)		at 1 month	No
Primary	Incidence of definite and/or probable stent thrombosis (ARC definition)		at 6 months	No
Primary	Incidence of definite and/or probable stent thrombosis (ARC definition)		at 12 months	No
Primary	Incidence of definite and/or probable stent thrombosis (ARC definition)		at 24 months	No
Secondary	Incidence of MACE. (MACE is defined as the composite of cardiac death, Q-wave myocardial infarction (MI), and unscheduled, ischemia driven revascularization of the target lesion.)		at 1 month	No
Secondary	Incidence of MACE. (MACE is defined as the composite of cardiac death, Q-wave myocardial infarction (MI), and unscheduled, ischemia driven revascularization of the target lesion.)		at 6 months	No
Secondary	Incidence of MACE. (MACE is defined as the composite of cardiac death, Q-wave myocardial infarction (MI), and unscheduled, ischemia driven revascularization of the target lesion.)		at 12 months	No
Secondary	Incidence of MACE. (MACE is defined as the composite of cardiac death, Q-wave myocardial infarction (MI), and unscheduled, ischemia driven revascularization of the target lesion.)		at 24 months	No
Secondary	Incidence of NACE (NACE is defined as the composite of cardiac death, MI (Q and non-Q-wave), ischemia driven revascularization of the target lesion and major bleeding (ACUITY criteria).)		at 1 month	No
Secondary	Incidence of NACE (NACE is defined as the composite of cardiac death, MI (Q and non-Q-wave), ischemia driven revascularization of the target lesion and major bleeding (ACUITY criteria).)		at 6 months	No
Secondary	Incidence of NACE (NACE is defined as the composite of cardiac death, MI (Q and non-Q-wave), ischemia driven revascularization of the target lesion and major bleeding (ACUITY criteria).)		at 12 months	No
Secondary	Incidence of NACE (NACE is defined as the composite of cardiac death, MI (Q and non-Q-wave), ischemia driven revascularization of the target lesion and major bleeding (ACUITY criteria).)		at 24 months	No