ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT00998127GCO 10-119609-36709-0421-F2L717/DGAAAE0348NCT00998127Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients
PARIS
Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients: An Observational Single-Arm Study (The PARIS Registry)Icahn School of Medicine at Mount SinaiOtherBristol-Myers SquibbIndustrySanofiIndustryYes
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.
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.
CompletedJune 2009March 2013December 2012ObservationalNoCohortProspectiveIncidence of Anti-platelet agent discontinuation/ interruption/ disruptionat 1 monthIncidence of Anti-platelet agent discontinuation/ interruption/ disruptionat 6 monthsIncidence of Anti-platelet agent discontinuation/ interruption/ disruptionat 12 monthsIncidence of Anti-platelet agent discontinuation/ interruption/ disruptionat 24 monthsIncidence of major and minor bleeding (according to TIMI and ACUITY definitions)at 1 monthIncidence of major and minor bleeding (according to TIMI and ACUITY definitions)at 6 monthsIncidence of major and minor bleeding (according to TIMI and ACUITY definitions)at 12 monthsIncidence of major and minor bleeding (according to TIMI and ACUITY definitions)at 24 monthsIncidence of definite and/or probable stent thrombosis (ARC definition)at 1 monthIncidence of definite and/or probable stent thrombosis (ARC definition)at 6 monthsIncidence of definite and/or probable stent thrombosis (ARC definition)at 12 monthsIncidence of definite and/or probable stent thrombosis (ARC definition)at 24 monthsIncidence 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 monthIncidence 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 monthsIncidence 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 monthsIncidence 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 monthsIncidence 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 monthIncidence 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 monthsIncidence 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 monthsIncidence 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 months5031Medication Non-adherenceStent Thrombosis
Subjects in any of the participating US or European sites who have undergone successful
stent implantation in a native coronary artery.
Non-Probability Sample
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.
All18 YearsN/ANoRoxana Mehran, MDPrincipal InvestigatorIcahn School of Medicine at Mount SinaiAntonio Colombo, MDPrincipal InvestigatorSan Raffaele Hospital (Milan, Italy)Washington Hospital CenterWashingtonDistrict of Columbia20010United StatesHeart Center of IndianaIndianapolisIndiana46290United StatesUniversity of KentuckyLexingtonKentucky40536United StatesWashington Adventist HospitalTakoma ParkMaryland20912United StatesMinneapolis Heart Institute FoundationMinneapolisMinnesota55407United StatesSaint Luke's/ Mid-America Heart InstituteKansas CityMissouri64111United StatesIcahn School of Medicine at Mount SinaiNew YorkNew York10029United StatesColumbia University Medical CenterNew YorkNew York10032United StatesLeBauer Cardiovascular Research FoundationGreensboroNorth Carolina27401United StatesGeisinger Medical Center ClinicDanvillePennsylvania17822United StatesHopital BichatParis75877FranceCharite - Campus Benjamin FranklinBerlin12203GermanyOnassis Cardiac Surgery CenterAthens176 74GreeceCareggi HospitalFlorence50134ItalySan Raffaele HospitalMilan20132ItalyFranceGermanyGreeceItalyUnited StatesFebruary 2016October 16, 2009October 19, 2009October 20, 2009February 10, 2016February 10, 2016February 11, 2016SponsorDual Anti-Platelet TherapyNon-adherenceMACENACEThrombosis