Clinical trial NCT03729401: Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND
Official title: Personalization of Long-Term Antiplatelet Therapy Using a Novel Combined Demographic/Pharmacogenomic Strategy - the RAPID EXTEND Randomized Study
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: Coronary Artery Disease
Myocardial Infarction
Keywords: 1-year post myocardial infarction
P2Y12 inhibitor
antiplatelet regimen
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2018-11-02
Enrollment: 390
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In patients after myocardial infarction (MI) (heart attacks) and treated with percutaneous coronary intervention (PCI), the current standard is dual antiplatelet therapy (DAPT), with aspirin and a P2Y12 receptor inhibitor, for 1 year of treatment. At 1 year, there are several options including: i) Ongoing DAPT (with aspirin and ticagrelor), ii) Selective treatment use of a P2Y12 inhibitor based on risk profiles.

This study is a pilot vanguard study to evaluate several strategies for choosing anti-platelet regimen among patients post MI and PCI at 1 year.

Detailed description: The present study is a pilot/vanguard 3-arm study that seeks to compare 3 possible strategies for patients that are 1 year post MI and PCI. The 3 randomized groups include: i) aspirin and ticagrelor 60 mg twice daily, ii) monotherapy with ticagrelor 60 mg twice daily and iii) a personalized arm (PA), where patients will get selective therapy based on demographic and genetic risks.

The PA group will use a modified DAPT score based on patient demographics to decide whether P2Y12 treatment is warranted. For those patients where treatment is warranted, a bedside genetic test will be used to determine whether they are carriers of at-risk genotypes, which put them at risk for under-responsiveness to clopidogrel (one of the specific P2Y12 inhibitors). Those identified as carriers will be treated with ticagrelor while non-carriers will be treated with clopidogrel.

The study will act as a vanguard study to prove feasibility of enrollment and document overall bleeding rates. The long-term goal of the study is determine whether a personalized approach will decrease bleeding versus an approach of DAPT with ticagrelor and versus an approach with ticagrelor monotherapy.

Eligibility criteria: Inclusion Criteria:

* \>50 years old at 1-year after myocardial infarction (non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI)) during which they had percutaneous coronary intervention (PCI)
* Compliant with dual antiplatelet therapy (DAPT) for ≥ 1 year without an ischemic or bleeding complication after PCI
* Still on DAPT regimen at enrollment
* Patients must have 1 of the following atherothrombotic risk enrichment criteria:

  i) Age≥ 65 years ii) Diabetes iii) 2nd Prior MI (\>1 year ago) iv) multi-vessel coronary disease v) creatinine clearance (CrCl) \<60 mL/min.

Exclusion Criteria:

* Intolerance to ticagrelor or clopidogrel
* \>18 months post percutaneous coronary intervention (PCI) and myocardial infarction (MI)
* Requirement of a P2Y12 inhibitor
* Requirement of oral anticoagulation
* Take concurrent CYP3A inducing drugs which may interact with ticagrelor (e.g. anti-epileptic drugs)
* History of stroke, TIA or intracranial bleed
* Recent GI bleed or major surgery
* Life expectancy of \< 1 year
* Platelet count \< 100,000/μl
* Bleeding diathesis
* On dialysis
* Severe liver disease
* At risk for bradycardia.

Primary outcomes:
measure: Bleeding Academic Research Consortium (BARC) Bleeding
timeFrame: 2 years post randomization
measure: Feasibility for Patient Enrollment and Follow-up - measured by number of patients enrolled and followed over 2 years
timeFrame: 2 years
Secondary outcomes:
measure: Thrombolysis in Myocardial Infarction (TIMI) bleeding
timeFrame: 1-3 years post randomization
measure: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding
timeFrame: 1-3 years post randomization
measure: All Cause Mortality
timeFrame: 1 - 3 years post randomization
measure: Cardiovascular Mortality
timeFrame: 1 -3 years post randomization
measure: Myocardial Infarction
timeFrame: 1 -3 years post randomization
measure: Stroke
timeFrame: 1-3 years
measure: Stent Thrombosis
timeFrame: 1 - 3 years post randomization
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Derek YF So, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372(19):1791-800. doi: 10.1056/NEJMoa1500857. Epub 2015 Mar 14.
citation: Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, Spertus JA, Steg PG, Cutlip DE, Rinaldi MJ, Camenzind E, Wijns W, Apruzzese PK, Song Y, Massaro JM, Mauri L; DAPT Study Investigators. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA. 2016 Apr 26;315(16):1735-49. doi: 10.1001/jama.2016.3775.
citation: Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016 Sep 6;134(10):e123-55. doi: 10.1161/CIR.0000000000000404. Epub 2016 Mar 29. No abstract available.