Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND

NCT03729401 | Terminated Phase 4 DMC

• 1 other identifier: 20180593
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease; Myocardial Infarction

Keywords

1-year post myocardial infarction; P2Y12 inhibitor; antiplatelet regimen

Outcome Measures

Primary Outcomes (2)

• Bleeding Academic Research Consortium (BARC) Bleeding

  BARC bleeding types 2,3 or 5

  2 years post randomization

• Feasibility for Patient Enrollment and Follow-up - measured by number of patients enrolled and followed over 2 years

  Number of participants enrolled and followed: Target of 260 patients over 2 years with over 90% follow-up (Vanguard Study target)

  2 years

Secondary Outcomes (7)

• Thrombolysis in Myocardial Infarction (TIMI) bleeding

  1-3 years post randomization

• Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding

  1-3 years post randomization

• All Cause Mortality

  1 - 3 years post randomization

• Cardiovascular Mortality

  1 -3 years post randomization

• Myocardial Infarction

  1 -3 years post randomization

Study Arms (3)

DAPT - Aspirin and Ticagrelor

ACTIVE COMPARATOR

As per results of the PEGASUS trial, patients will be treated with aspirin 81mg daily and ticagrelor 60mg twice daily

Drug: Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily

Ticagrelor Monotherapy

EXPERIMENTAL

Patients will only receive ticagrelor 60mg twice daily.

Drug: Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily

Personalized Therapy Arm

EXPERIMENTAL

Patients allocated to the personalized arm (PA) will have a DAPT score calculated. For those with a score of \< 2, only aspirin at 81 mg daily will be prescribed. For those with a score of ≥ 2, P2Y12 inhibitor choice will be dependent on carrier status of CYP2C19 LOF alleles. Heterozygous or homozygous carriers will receive be prescribed ticagrelor 60mg twice daily and non-carriers with will be prescribed clopidogrel 75mg daily.

Drug: Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily

Interventions

Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily DRUG

DAPT with aspirin and ticagrelor

Also known as: ASA, Brilinta

DAPT - Aspirin and Ticagrelor

Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily DRUG

Ticagrelor monotherapy

Also known as: Brilinta

Ticagrelor Monotherapy

Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily DRUG

Personalized therapy based on risk score and genotyping

Also known as: ASA, Brilinta, Plavix

Personalized Therapy Arm

Eligibility Criteria

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

You may qualify if:

• \>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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

Location

Related Publications (3)

• 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.

  PMID: 25773268 BACKGROUND

• 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. Erratum In: JAMA. 2016 Jul 19;316(3):350. doi: 10.1001/jama.2016.6123. JAMA. 2016 Jul 19;316(3):350. doi: 10.1001/jama.2016.9558.

  PMID: 27022822 BACKGROUND

• 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. Erratum In: Circulation. 2016 Sep 6;134(10):e192-4. doi: 10.1161/CIR.0000000000000452.

  PMID: 27026020 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Infarction

Interventions

2'-deoxythymidylyl-(3'-5')-2'-deoxyadenosine; Aspirin; Ticagrelor; Clopidogrel

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; 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; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Derek YF So, MD FRCPC

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: November 2, 2018
• Study Start: August 22, 2019
• Primary Completion: March 31, 2024
• Study Completion: February 26, 2026
• Last Updated: May 6, 2026

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)