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Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND (RAPID EXTEND)

Primary Purpose

Coronary Artery Disease, Myocardial Infarction

Status
Suspended
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily
Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily
Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily
Sponsored by
Ottawa Heart Institute Research Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring 1-year post myocardial infarction, P2Y12 inhibitor, antiplatelet regimen

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Ottawa Heart Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

DAPT - Aspirin and Ticagrelor

Ticagrelor Monotherapy

Personalized Therapy Arm

Arm Description

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

Patients will only receive ticagrelor 60mg twice daily.

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.

Outcomes

Primary Outcome Measures

Bleeding Academic Research Consortium (BARC) Bleeding
BARC bleeding types 2,3 or 5
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)

Secondary Outcome Measures

Thrombolysis in Myocardial Infarction (TIMI) bleeding
Incidence of TIMI bleeding - major and minor
Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding
Incidence of GUSTO bleeding - severe, moderate, mild
All Cause Mortality
Death due to any cause
Cardiovascular Mortality
Death due to cardiovascular cause
Myocardial Infarction
Myocardial infarction as defined by the 3rd universal definition on infarction
Stroke
Strokes defined as focal neurological deficit of >24 hrs and confirmed by imaging
Stent Thrombosis
Probable and definite stent thrombosis per ARC definition

Full Information

First Posted
October 15, 2018
Last Updated
April 5, 2023
Sponsor
Ottawa Heart Institute Research Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03729401
Brief Title
Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND
Acronym
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Suspended
Why Stopped
Testing supplies unavailable.
Study Start Date
August 22, 2019 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Heart Institute Research Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Myocardial Infarction
Keywords
1-year post myocardial infarction, P2Y12 inhibitor, antiplatelet regimen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Masking Description
Double (Investigator, Outcomes Assessor)
Allocation
Randomized
Enrollment
390 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DAPT - Aspirin and Ticagrelor
Arm Type
Active Comparator
Arm Description
As per results of the PEGASUS trial, patients will be treated with aspirin 81mg daily and ticagrelor 60mg twice daily
Arm Title
Ticagrelor Monotherapy
Arm Type
Experimental
Arm Description
Patients will only receive ticagrelor 60mg twice daily.
Arm Title
Personalized Therapy Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily
Other Intervention Name(s)
ASA, Brilinta
Intervention Description
DAPT with aspirin and ticagrelor
Intervention Type
Drug
Intervention Name(s)
Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily
Other Intervention Name(s)
Brilinta
Intervention Description
Ticagrelor monotherapy
Intervention Type
Drug
Intervention Name(s)
Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily
Other Intervention Name(s)
ASA, Brilinta, Plavix
Intervention Description
Personalized therapy based on risk score and genotyping
Primary Outcome Measure Information:
Title
Bleeding Academic Research Consortium (BARC) Bleeding
Description
BARC bleeding types 2,3 or 5
Time Frame
2 years post randomization
Title
Feasibility for Patient Enrollment and Follow-up - measured by number of patients enrolled and followed over 2 years
Description
Number of participants enrolled and followed: Target of 260 patients over 2 years with over 90% follow-up (Vanguard Study target)
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Thrombolysis in Myocardial Infarction (TIMI) bleeding
Description
Incidence of TIMI bleeding - major and minor
Time Frame
1-3 years post randomization
Title
Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding
Description
Incidence of GUSTO bleeding - severe, moderate, mild
Time Frame
1-3 years post randomization
Title
All Cause Mortality
Description
Death due to any cause
Time Frame
1 - 3 years post randomization
Title
Cardiovascular Mortality
Description
Death due to cardiovascular cause
Time Frame
1 -3 years post randomization
Title
Myocardial Infarction
Description
Myocardial infarction as defined by the 3rd universal definition on infarction
Time Frame
1 -3 years post randomization
Title
Stroke
Description
Strokes defined as focal neurological deficit of >24 hrs and confirmed by imaging
Time Frame
1-3 years
Title
Stent Thrombosis
Description
Probable and definite stent thrombosis per ARC definition
Time Frame
1 - 3 years post randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Derek YF So, MD FRCPC
Organizational Affiliation
Ottawa Heart Institute Research Corporation
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y4W7
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25773268
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.
Results Reference
background
PubMed Identifier
27022822
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. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.
Results Reference
background
PubMed Identifier
27026020
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. Erratum In: Circulation. 2016 Sep 6;134(10):e192-4.
Results Reference
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Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND

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