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

NCT03224923 | Terminated Phase 4 DMC

• 1 other identifier: 20170341
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Stable Coronary Syndrome; Percutaneous Coronary Intervention; Antiplatelet Therapy; Ticagrelor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Platelet Reactivity Index (PRI) as a continuous variable

  1 month

• ADP-induced Aggregation (AU) as a continuous variable

  1 month

• Bleeding according to Bleeding Academic Research Consortium (BARC) criteria

  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

  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

  1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years

Other Outcomes (2)

• Cost

  1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years

• Genetic factors associated to outcomes

  1 month, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years

Study Arms (2)

Personalized Treatment Algorithm

EXPERIMENTAL

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; Drug: Clopidogrel 75mg; Drug: Aspirin 81 mg

Long-Term Ticagrelor

ACTIVE COMPARATOR

Patients will be given 60mg Ticagrelor twice daily with no aspirin

Drug: Ticagrelor 60mg

Interventions

Ticagrelor 60mg DRUG

twice daily

Long-Term Ticagrelor; Personalized Treatment Algorithm

Clopidogrel 75mg DRUG

once daily

Personalized Treatment Algorithm

Aspirin 81 mg DRUG

once daily

Personalized Treatment Algorithm

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• nd prior MI (\> 1 year ago)
• multi-vessel coronary disease
• Creatinine Clearance \< 60mL/min

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

Location

MeSH Terms

Interventions

Ticagrelor; Clopidogrel; Aspirin

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Derek So, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 21, 2017
• Study Start: August 18, 2017
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: July 19, 2019

Record last verified: 2019-07

Locations

CA (1)