Clinical trial NCT03224923: A Novel Strategy For Personalized Long-Term Dual Antiplatelet Therapy (RAPID EXTEND PILOT STUDY)
Official title: Reassessment of Long-Term Dual Anti-Platelet Therapy Using InDividualized Strategies - Using a Novel Combined Demographic and Pharmacogenomic Strategy: The RAPID EXTEND Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Stable Coronary Syndrome
Percutaneous Coronary Intervention
Antiplatelet Therapy
Ticagrelor
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2017-07-21
Enrollment: 5
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 with heart attacks, the current standard of care is to restore blood flow through percutaneous coronary intervention (PCI). This is done using stents (metal meshes) that opens up blockages. Following PCI, standard preventative drug treatment includes the use of dual antiplatelet therapy (DAPT) using both aspirin and a platelet P2Y12 receptor inhibitor (Ticagrelor 90 mg twice a day or Clopidogrel 75 mg once a day) for one year to prevent clotting that can result in additional heart attacks, sudden clotting of stents or death.

New studies have shown that there is a benefit to continuing DAPT beyond this one year mark. Longer-term DAPT has been shown to reduce ischemic events (heart attack, stroke) but increase the risk of bleeding. Present guidelines state that the decision to continue DAPT beyond the one year mark should be made on an individualized basis.

The present study is a "pilot study" that seeks to compare Long-Term use of Ticagrelor (LTT) versus a Personalized Approach (PA). We will be recruiting patients who have been stable (free of ischemic or bleeding outcomes) on DAPT for 1 year after initial presentation with a heart attack.

The PA group will use a modified DAPT score based on patient demographics to decide whether treatment is warranted. Patient will also undergo bedside genetic testing to identify potential at-risk genes. Those identified as carriers will be treated with ticagrelor while non-carriers will be treated with clopidogrel.

The present study will determine whether a personalized approach will decrease bleeding versus an approach of universal ticagrelor use.

The hypothesis is that patients receiving a personalized strategy will have a decreased risk of bleeding.


Eligibility criteria: Inclusion Criteria:

* non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) at presentation for index PCI who have successfully completed \>1-year follow-up of RAPID MANAGE or TAILOR-PCI trials without having incurred an ischemic or bleeding outcome while on DAPT
* Patients with DAPT interruption after 1 year will be eligible, if within 3 years of index MI

Patients must also have 1 of the following atherothrombotic risk enrichment criteria:

* age ≥ 65 years
* diabetes
* 2nd prior MI (\> 1 year ago)
* multi-vessel coronary disease
* Creatinine Clearance \< 60mL/min

Exclusion Criteria:

Patients will be excluded from the study if they:

* refuse consent
* are \> 3 years post MI
* are deemed to require a P2Y12 inhibitor
* require oral anticoagulation
* have a history of stroke, transient ischemic attack (TIA) or intracranial bleed
* have had a recent GI bleed or major surgery
* have a life expectancy of \< 1 year
* have a platelet count \< 100,000/μl
* have a bleeding diathesis
* have hematocrit \< 30% or \> 52%
* are on dialysis or have severe liver disease
* are at risk for bradycardia

Primary outcomes:
measure: Proportion of Patients with Decreased Bleeding Risk
timeFrame: 1 month
Secondary outcomes:
measure: Platelet Reactivity Index (PRI) as a continuous variable
timeFrame: 1 month
measure: ADP-induced Aggregation (AU) as a continuous variable
timeFrame: 1 month
measure: Bleeding according to Bleeding Academic Research Consortium (BARC) criteria
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Bleeding according to Thrombolysis in Myocardial Infarction (TIMI) score
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Bleeding according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Ischemic Endpoints (To be collected but blinded to investigators, as this data will be carried from the pilot study into a future definitive clinical trial).
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Ischemic Endpoints (To be collected but blinded to investigators, as this data will be carried from the pilot study into a future definitive clinical trial).
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Ischemic Endpoints (To be collected but blinded to investigators, as this data will be carried from the pilot study into a future definitive clinical trial).
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Ischemic Endpoints (To be collected but blinded to investigators, as this data will be carried from the pilot study into a future definitive clinical trial).
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
Other outcomes:
measure: Cost
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
measure: Genetic factors associated to outcomes
timeFrame: 1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Derek So, MD
role: PRINCIPAL_INVESTIGATOR
References: