Back to resultsStudy of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery (INTREPID)
Primary Purpose
Myocardial Injury
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
ticagrelor
aspirin
Sponsored by
About this trial
This is an interventional prevention trial for Myocardial Injury focused on measuring ticagrelor, non-cardiac surgery, elevated troponin, myocardial injury
Eligibility Criteria
Inclusion Criteria:
- Written informed consent before any study related procedures are performed.
- A qualifying post-operative T or I troponin elevation (≥2x ULN of assay within 7 days of index surgery and during the index hospitalization).
- Men and women ≥40 years of age if troponin elevation was identified as part of routine post-operative clinical care OR
- Men and women ≥55 years of age if troponin elevation was identified post-operatively as part of screening for the study.
- Undergone non-cardiac surgery requiring an overnight hospital stay.
- Women of childbearing potential who are sexually active must have a negative pregnancy test at enrollment and agree to use adequate contraception from screening until 30 days after receiving the last dose of study drug.
- Able to be randomized within 35 days following the index surgery.
Exclusion Criteria:
- Post-operative ST-elevation Myocardial Infarction (STEMI).
Post-operative high-risk non-STEMI, defined as patients with elevated troponin with either:
- active Ischemic EKG changes (≥2 mm of ST-segment depression in at least 2 adjacent leads)
- ongoing hemodynamic instability thought to be ischemia mediated or
- persistent anginal symptoms.
- Planned or urgent coronary angiography/revascularization.
- A current or ongoing indication for dual antiplatelet therapy (DAPT) as determined by the patient's physician.
- History of intracranial hemorrhage
- Bleeding disorder or active bleeding that prevents ticagrelor or aspirin administration.
- Taking any of the following medications at the time of randomization: vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban , fondaparinux, cilostazol, vorapaxar or LMWHs.
- Renal dialysis.
- Hepatic impairment with transaminase ≥3x ULN at time of randomization.
- Known contra-indication for use of ticagrelor.
- Estimated life expectancy of <1 year.
- Enrolled in another ongoing drug or device research protocol
- A definite non-ischemic explanation for troponin elevation, such as myocarditis or pulmonary embolism.
- A documented hypersensitivity to aspirin.
- Hypersensitivity to ticagrelor or any component of the product.
- Neurological or ophthalmic surgery during the index hospitalization.
- Patients taking strong CYP3A inhibitors and/or CYP3A inducers that cannot be stopped for the course of the study.
Sites / Locations
- University of South Alabama Health System
- Arkansas Site Management Service, LLC
- University of Florida College of Medicine - Jacksonville
- Florida Hospital Orthopaedic Institute and Fracture Care Center
- University of South Florida
- Central Georgia Heart Center
- Saint Vincent Medical Group
- University of Kentucky
- Sinai Hospital of Baltimore
- McLaren Bay Region
- Henry Ford Hospital
- McLaren Macomb
- University of Minnesota
- New York University School of Medicine
- Cincinnati VA Medical Center
- VA Medical Center - Cleveland Louis Stokes
- MetroHealth Medical Center
- Cleveland Clinic
- Miami Valley Hospital
- Oklahoma Heart Institute
- Oregon Health and Science University
- VA North Texas Health Care System
- University of Texas Health Science Center at Houston
- Overlake Hospital Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ticagrelor
aspirin
Arm Description
ticagrelor 90mg bid
Patients in the aspirin arm will receive aspirin 81 mg daily orally
Outcomes
Primary Outcome Measures
Major Adverse Cardiovascular Events
Time to first occurence of the composite of Cardiovascular Death, Non-fatal Myocardial Infarction, Coronary Revascularization or Non-fatal Stroke. The number of patients with events is reported.
Secondary Outcome Measures
Cardiovascular Death
Time to first occurence of Cardiovascular death. The number of patients with events was reported.
Non-fatal Myocardial Infarction or Coronary Revascularization
Time to first occurence of Non-fatal myocardial infarction or coronary revascularization. The number of participants with events was reported.
All-cause Death
Time to first occurence of All-cause death. The number of participants with events was reported.
Non-fatal Stroke
Time to first occurence of Non-fatal stroke. The number of participants with events was reported.
Full Information
NCT ID
NCT02291419
First Posted
November 5, 2014
Last Updated
February 8, 2017
Sponsor
The Cleveland Clinic
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT02291419
Brief Title
Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery
Acronym
INTREPID
Official Title
An Open Label, Randomized Study to Determine the Rate of Cardiovascular Events at 1 yr for Patients With Elevated Troponins Post Major Non-cardiac Surgery and the Impact of Ticagrelor vs Aspirin on the Occurrence of Cardiovascular Events
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Enrollment expectations were not met
Study Start Date
July 2015 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic
Collaborators
AstraZeneca
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this pilot study is to establish the rate of cardiovascular events in patients with elevated troponins levels after major, non-cardiac surgery and to evaluate the efficacy and safety of FDA approved study drug (ticagrelor) compared to aspirin in these patients.
Data from current studies suggest that myocardial injury detected by minor elevations in troponin levels within 3 days after non-cardiac surgery may occur in 10-24% of patients and is associated with an increased risk of mortality at 30 days and 1 year. There are no current guidelines for care of patients with elevated troponin levels in the absence of acute coronary syndrome. This study will assess if the increased risk of these patients is modifiable by an anti-platelet medication and evaluate the safety of this medication.
Patients will be randomized in an open label fashion to receive ticagrelor (anti-platelet medication) or 81 mg. aspirin. Patients will be followed on study treatment for 12 months, with the last contact at one month post treatment discontinuation.
Detailed Description
The objective of this pilot study is to establish the rate of cardiovascular events in patients with elevated troponins levels post major, non-cardiac surgery and to evaluate the efficacy and safety of ticagrelor treatment compared to aspirin in these patients.
Data from current studies suggest that myocardial injury detected by minor elevations in troponin levels within 3 days after non-cardiac surgery may occur in 10-24% of patients and is associated with an increased risk of mortality at 30 days and 1 year. There are no current guidelines for care of patients with elevated troponin levels in the absence of acute coronary syndrome (ACS) and it is not certain if this is a modifiable disease process. Ticagrelor is a direct, reversible inhibitor of the platelet P2Y12ADP-receptor. It has been shown to be superior to clopidogrel in the setting of ACS. The clinical benefit of treating patients with port-operative troponin elevation with antiplatelet agents remains unexplored. The short half-life of ticagrelor makes it favorable to use in this setting.
This is an open label, randomized, parallel group study comparing ticagrelor to aspirin in patients who experience troponin elevations post major non-cardiac surgery. Patients will be randomized in an open-label fashion to receive either ticagrelor 90 mg twice daily or aspirin 81 mg once daily. Patients will be followed for 13 months post randomization (12 months of treatment and a phone call 30 days after study drug discontinuation). The maximum duration of treatment will be 12 months.
Follow-up visits will occur at Month 1, Month 6, and Month 12. Phone calls will be made at Month 3, Month 9, and at 30 days after study drug discontinuation.
Up to 1000 patients with post-operative troponin elevation ≥2x ULN within first 7 postoperative days, will be enrolled in the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Injury
Keywords
ticagrelor, non-cardiac surgery, elevated troponin, myocardial injury
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ticagrelor
Arm Type
Experimental
Arm Description
ticagrelor 90mg bid
Arm Title
aspirin
Arm Type
Active Comparator
Arm Description
Patients in the aspirin arm will receive aspirin 81 mg daily orally
Intervention Type
Drug
Intervention Name(s)
ticagrelor
Other Intervention Name(s)
Brilinta
Intervention Description
ticagrelor 90 mg bid
Intervention Type
Drug
Intervention Name(s)
aspirin
Other Intervention Name(s)
Bayer, ASA
Intervention Description
aspirin 81 mg daily
Primary Outcome Measure Information:
Title
Major Adverse Cardiovascular Events
Description
Time to first occurence of the composite of Cardiovascular Death, Non-fatal Myocardial Infarction, Coronary Revascularization or Non-fatal Stroke. The number of patients with events is reported.
Time Frame
up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Secondary Outcome Measure Information:
Title
Cardiovascular Death
Description
Time to first occurence of Cardiovascular death. The number of patients with events was reported.
Time Frame
Up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Title
Non-fatal Myocardial Infarction or Coronary Revascularization
Description
Time to first occurence of Non-fatal myocardial infarction or coronary revascularization. The number of participants with events was reported.
Time Frame
up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Title
All-cause Death
Description
Time to first occurence of All-cause death. The number of participants with events was reported.
Time Frame
up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Title
Non-fatal Stroke
Description
Time to first occurence of Non-fatal stroke. The number of participants with events was reported.
Time Frame
up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Other Pre-specified Outcome Measures:
Title
The Number of Participants With Bleeding According to Bleeding Academic Research Consortium (BARC) Definitions
Time Frame
up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent before any study related procedures are performed.
A qualifying post-operative T or I troponin elevation (≥2x ULN of assay within 7 days of index surgery and during the index hospitalization).
Men and women ≥40 years of age if troponin elevation was identified as part of routine post-operative clinical care OR
Men and women ≥55 years of age if troponin elevation was identified post-operatively as part of screening for the study.
Undergone non-cardiac surgery requiring an overnight hospital stay.
Women of childbearing potential who are sexually active must have a negative pregnancy test at enrollment and agree to use adequate contraception from screening until 30 days after receiving the last dose of study drug.
Able to be randomized within 35 days following the index surgery.
Exclusion Criteria:
Post-operative ST-elevation Myocardial Infarction (STEMI).
Post-operative high-risk non-STEMI, defined as patients with elevated troponin with either:
active Ischemic EKG changes (≥2 mm of ST-segment depression in at least 2 adjacent leads)
ongoing hemodynamic instability thought to be ischemia mediated or
persistent anginal symptoms.
Planned or urgent coronary angiography/revascularization.
A current or ongoing indication for dual antiplatelet therapy (DAPT) as determined by the patient's physician.
History of intracranial hemorrhage
Bleeding disorder or active bleeding that prevents ticagrelor or aspirin administration.
Taking any of the following medications at the time of randomization: vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban , fondaparinux, cilostazol, vorapaxar or LMWHs.
Renal dialysis.
Hepatic impairment with transaminase ≥3x ULN at time of randomization.
Known contra-indication for use of ticagrelor.
Estimated life expectancy of <1 year.
Enrolled in another ongoing drug or device research protocol
A definite non-ischemic explanation for troponin elevation, such as myocarditis or pulmonary embolism.
A documented hypersensitivity to aspirin.
Hypersensitivity to ticagrelor or any component of the product.
Neurological or ophthalmic surgery during the index hospitalization.
Patients taking strong CYP3A inhibitors and/or CYP3A inducers that cannot be stopped for the course of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Venu Menon, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of South Alabama Health System
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36617
Country
United States
Facility Name
Arkansas Site Management Service, LLC
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72211
Country
United States
Facility Name
University of Florida College of Medicine - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Florida Hospital Orthopaedic Institute and Fracture Care Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33060
Country
United States
Facility Name
Central Georgia Heart Center
City
Macon
State/Province
Georgia
ZIP/Postal Code
31201
Country
United States
Facility Name
Saint Vincent Medical Group
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
McLaren Bay Region
City
Bay City
State/Province
Michigan
ZIP/Postal Code
48708
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
McLaren Macomb
City
Mount Clemens
State/Province
Michigan
ZIP/Postal Code
48043
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cincinnati VA Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Facility Name
VA Medical Center - Cleveland Louis Stokes
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MetroHealth Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Oklahoma Heart Institute
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
VA North Texas Health Care System
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Overlake Hospital Medical Center
City
Bellevue
State/Province
Washington
ZIP/Postal Code
98004
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19717846
Citation
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.
Results Reference
background
PubMed Identifier
22706835
Citation
Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012 Jun 6;307(21):2295-304. doi: 10.1001/jama.2012.5502. Erratum In: JAMA. 2012 Jun 27;307(24):2590.
Results Reference
background
PubMed Identifier
18479744
Citation
POISE Study Group; Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Malaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. doi: 10.1016/S0140-6736(08)60601-7. Epub 2008 May 12.
Results Reference
background
PubMed Identifier
26366956
Citation
Horr S, Reed G, Menon V. Troponin elevation after noncardiac surgery: Significance and management. Cleve Clin J Med. 2015 Sep;82(9):595-602. doi: 10.3949/ccjm.82a.15076.
Results Reference
derived
Learn more about this trial
Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery
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