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

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Sanofi
Information provided by (Responsible Party):
Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00998127
First received: October 16, 2009
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

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.


Condition
Medication Non-adherence
Stent Thrombosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients: An Observational Single-Arm Study (The PARIS Registry)

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Incidence of Anti-platelet agent discontinuation/ interruption/ disruption [ Time Frame: at 1 month ] [ Designated as safety issue: No ]
  • Incidence of Anti-platelet agent discontinuation/ interruption/ disruption [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Incidence of Anti-platelet agent discontinuation/ interruption/ disruption [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • Incidence of Anti-platelet agent discontinuation/ interruption/ disruption [ Time Frame: at 24 months ] [ Designated as safety issue: No ]
  • Incidence of major and minor bleeding (according to TIMI and ACUITY definitions) [ Time Frame: at 1 month ] [ Designated as safety issue: No ]
  • Incidence of major and minor bleeding (according to TIMI and ACUITY definitions) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Incidence of major and minor bleeding (according to TIMI and ACUITY definitions) [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • Incidence of major and minor bleeding (according to TIMI and ACUITY definitions) [ Time Frame: at 24 months ] [ Designated as safety issue: No ]
  • Incidence of definite and/or probable stent thrombosis (ARC definition) [ Time Frame: at 1 month ] [ Designated as safety issue: No ]
  • Incidence of definite and/or probable stent thrombosis (ARC definition) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Incidence of definite and/or probable stent thrombosis (ARC definition) [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • Incidence of definite and/or probable stent thrombosis (ARC definition) [ Time Frame: at 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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.) [ Time Frame: at 1 month ] [ Designated as safety issue: No ]
  • 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.) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • 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.) [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • 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.) [ Time Frame: at 24 months ] [ Designated as safety issue: No ]
  • 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).) [ Time Frame: at 1 month ] [ Designated as safety issue: No ]
  • 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).) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • 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).) [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • 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).) [ Time Frame: at 24 months ] [ Designated as safety issue: No ]

Enrollment: 5033
Study Start Date: June 2009
Study Completion Date: March 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Detailed 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 for the prevention of thrombotic events in patients who present with unstable coronary symptoms; in particular, patients who are to receive 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects in any of the participating US or European sites who have undergone successful stent implantation in a native coronary artery.

Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00998127

Locations
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Indiana
Heart Center of Indiana
Indianapolis, Indiana, United States, 46290
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Washington Adventist Hospital
Takoma Park, Maryland, United States, 20912
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
United States, Missouri
Saint Luke's/ Mid-America Heart Institute
Kansas City, Missouri, United States, 64111
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, North Carolina
LeBauer Cardiovascular Research Foundation
Greensboro, North Carolina, United States, 27401
United States, Pennsylvania
Geisinger Medical Center Clinic
Danville, Pennsylvania, United States, 17822
France
Hopital Bichat
Paris, France, 75877
Germany
Charite - Campus Benjamin Franklin
Berlin, Germany, 12203
Greece
Onassis Cardiac Surgery Center
Athens, Greece, 176 74
Italy
Careggi Hospital
Florence, Italy, 50134
San Raffaele Hospital
Milan, Italy, 20132
Sponsors and Collaborators
Mount Sinai School of Medicine
Bristol-Myers Squibb
Sanofi
Investigators
Principal Investigator: Roxana Mehran, MD Mount Sinai School of Medicine
Principal Investigator: Antonio Colombo, MD San Raffaele Hospital (Milan, Italy)
  More Information

No publications provided by Mount Sinai School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00998127     History of Changes
Other Study ID Numbers: GCO 10-1196, 09-367, 09-0421-F2L, 717/DG, AAAE0348
Study First Received: October 16, 2009
Last Updated: October 25, 2013
Health Authority: United States: Institutional Review Board
France: Institutional Ethical Committee
Germany: Ethics Commission
Italy: Ethics Committee
Greece: Ethics Committee

Keywords provided by Mount Sinai School of Medicine:
Dual Anti-Platelet Therapy
Non-adherence
MACE
NACE

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 16, 2014