A Novel Strategy For Personalized Long-Term Dual Antiplatelet Therapy (RAPID EXTEND PILOT STUDY)

Reassessment of Long-Term Dual Anti-Platelet Therapy Using InDividualized Strategies - Using a Novel Combined Demographic and Pharmacogenomic Strategy: The RAPID EXTEND Pilot Study

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.

Study Overview

• Status: Terminated
• Conditions: Percutaneous Coronary Intervention; Ticagrelor; Antiplatelet Therapy; Stable Coronary Syndrome
• Intervention / Treatment: Drug: Ticagrelor 60mg; Drug: Clopidogrel 75mg; Drug: Aspirin 81 mg

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y4W7
      • University of Ottawa Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Personalized Treatment Algorithm; A DAPT score using various patient demographics will be calculated: If score under 2, patients will receive only aspirin 81 mg once daily If DAPT score is ≥ 2; A point-of-care bedside genetic test using a buccal swab will be conducted in order to determine medication regimen; Those with a positive genetic test (presence of CYP2C19*2 or CYP2C19*3), will receive 60mg Ticagrelor twice daily; Those with a negative genetic test (absence of CYP2C19*2/*3) will receive 75mg clopidogrel once daily	Drug: Ticagrelor 60mg; twice daily; Drug: Clopidogrel 75mg; once daily; Drug: Aspirin 81 mg; once daily
ACTIVE_COMPARATOR: Long-Term Ticagrelor; Patients will be given 60mg Ticagrelor twice daily with no aspirin	Drug: Ticagrelor 60mg; twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients with Decreased Bleeding Risk	The primary endpoint is the proportion of patients with low on-treatment platelet reactivity (LPR) in the PA group compared to the LTT group at 1 month.; P2Y12 reactivity units (PRU) as a continuous variable will be measured using a VerifyNow P2Y12 assay; a PRU value of < 85 is associated with increased bleeding risk	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Reactivity Index (PRI) as a continuous variable	Platelet function as measured by Vasodilator-stimulated phosphoprotein (VASP); a PRI of < 16% is associated with increased bleeding risk	1 month
ADP-induced Aggregation (AU) as a continuous variable	Platelet function as measured by Multiplate analyzer; an AU of < 19 is associated with increased bleeding risk	1 month
Bleeding according to Bleeding Academic Research Consortium (BARC) criteria	the incidence and severity of bleeding as defined by BARC classification system	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
Bleeding according to Thrombolysis in Myocardial Infarction (TIMI) score	the incidence and severity of bleeding as defined by TIMI classification systems	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
Bleeding according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria	the incidence and severity of bleeding as defined by GUSTO classification systems	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
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).	all-cause mortality incidence	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
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).	recurrent myocardial infarction (MI) incidence	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
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).	stroke incidence	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
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).	stent thrombosis incidence	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost	Evaluate cost involved in each strategy	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years
Genetic factors associated to outcomes	Exploratory analysis of other potential genetic variants to outcomes	1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 18, 2017
• Primary Completion (ACTUAL): September 30, 2018
• Study Completion (ACTUAL): September 30, 2018

Study Registration Dates

• First Submitted: July 14, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (ACTUAL): July 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 19, 2019
• Last Update Submitted That Met QC Criteria: July 17, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor; Clopidogrel
• Other Study ID Numbers: 20170341

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No