We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery (INTREPID)

This study has been terminated.
(Enrollment expectations were not met)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02291419
First Posted: November 14, 2014
Last Update Posted: February 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Venu Menon, The Cleveland Clinic
  Purpose

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.


Condition Intervention Phase
Myocardial Injury Drug: ticagrelor Drug: aspirin Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Venu Menon, The Cleveland Clinic:

Primary Outcome Measures:
  • Major Adverse Cardiovascular Events [ Time Frame: up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months. ]
    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 Frame: Up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months. ]
    Time to first occurence of Cardiovascular death. The number of patients with events was reported.

  • Non-fatal Myocardial Infarction or Coronary Revascularization [ Time Frame: up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months. ]
    Time to first occurence of Non-fatal myocardial infarction or coronary revascularization. The number of participants with events was reported.

  • All-cause Death [ Time Frame: up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months. ]
    Time to first occurence of All-cause death. The number of participants with events was reported.

  • Non-fatal Stroke [ Time Frame: up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months. ]
    Time to first occurence of Non-fatal stroke. The number of participants with events was reported.


Other Outcome Measures:
  • 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. ]

Enrollment: 6
Study Start Date: July 2015
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ticagrelor
ticagrelor 90mg bid
Drug: ticagrelor
ticagrelor 90 mg bid
Other Name: Brilinta
Active Comparator: aspirin
Patients in the aspirin arm will receive aspirin 81 mg daily orally
Drug: aspirin
aspirin 81 mg daily
Other Name: Bayer, ASA

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent before any study related procedures are performed.
  2. A qualifying post-operative T or I troponin elevation (≥2x ULN of assay within 7 days of index surgery and during the index hospitalization).
  3. Men and women ≥40 years of age if troponin elevation was identified as part of routine post-operative clinical care OR
  4. Men and women ≥55 years of age if troponin elevation was identified post-operatively as part of screening for the study.
  5. Undergone non-cardiac surgery requiring an overnight hospital stay.
  6. 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.
  7. Able to be randomized within 35 days following the index surgery.

Exclusion Criteria:

  1. Post-operative ST-elevation Myocardial Infarction (STEMI).
  2. Post-operative high-risk non-STEMI, defined as patients with elevated troponin with either:

    1. active Ischemic EKG changes (≥2 mm of ST-segment depression in at least 2 adjacent leads)
    2. ongoing hemodynamic instability thought to be ischemia mediated or
    3. persistent anginal symptoms.
  3. Planned or urgent coronary angiography/revascularization.
  4. A current or ongoing indication for dual antiplatelet therapy (DAPT) as determined by the patient's physician.
  5. History of intracranial hemorrhage
  6. Bleeding disorder or active bleeding that prevents ticagrelor or aspirin administration.
  7. Taking any of the following medications at the time of randomization: vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban , fondaparinux, cilostazol, vorapaxar or LMWHs.
  8. Renal dialysis.
  9. Hepatic impairment with transaminase ≥3x ULN at time of randomization.
  10. Known contra-indication for use of ticagrelor.
  11. Estimated life expectancy of <1 year.
  12. Enrolled in another ongoing drug or device research protocol
  13. A definite non-ischemic explanation for troponin elevation, such as myocarditis or pulmonary embolism.
  14. A documented hypersensitivity to aspirin.
  15. Hypersensitivity to ticagrelor or any component of the product.
  16. Neurological or ophthalmic surgery during the index hospitalization.
  17. Patients taking strong CYP3A inhibitors and/or CYP3A inducers that cannot be stopped for the course of the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02291419


  Hide Study Locations
Locations
United States, Alabama
University of South Alabama Health System
Mobile, Alabama, United States, 36617
United States, Arkansas
Arkansas Site Management Service, LLC
Little Rock, Arkansas, United States, 72211
United States, Florida
University of Florida College of Medicine - Jacksonville
Jacksonville, Florida, United States, 32209
Florida Hospital Orthopaedic Institute and Fracture Care Center
Orlando, Florida, United States, 32804
University of South Florida
Tampa, Florida, United States, 33060
United States, Georgia
Central Georgia Heart Center
Macon, Georgia, United States, 31201
United States, Indiana
Saint Vincent Medical Group
Indianapolis, Indiana, United States, 46260
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
United States, Michigan
McLaren Bay Region
Bay City, Michigan, United States, 48708
Henry Ford Hospital
Detroit, Michigan, United States, 48202
McLaren Macomb
Mount Clemens, Michigan, United States, 48043
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
United States, Ohio
Cincinnati VA Medical Center
Cincinnati, Ohio, United States, 45220
VA Medical Center - Cleveland Louis Stokes
Cleveland, Ohio, United States, 44106
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Miami Valley Hospital
Dayton, Ohio, United States, 45409
United States, Oklahoma
Oklahoma Heart Institute
Tulsa, Oklahoma, United States, 74104
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Texas
VA North Texas Health Care System
Dallas, Texas, United States, 75216
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
United States, Washington
Overlake Hospital Medical Center
Bellevue, Washington, United States, 98004
Sponsors and Collaborators
The Cleveland Clinic
AstraZeneca
Investigators
Principal Investigator: Venu Menon, MD The Cleveland Clinic
  More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Venu Menon, MD, FACC, FAHA, Director CICU, CEC-C5, Fellowship Program Cardiovascular Imaging, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT02291419     History of Changes
Other Study ID Numbers: CCAZ-2014
First Submitted: November 5, 2014
First Posted: November 14, 2014
Results First Submitted: February 8, 2017
Results First Posted: February 9, 2017
Last Update Posted: February 9, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Venu Menon, The Cleveland Clinic:
ticagrelor
non-cardiac surgery
elevated troponin
myocardial injury

Additional relevant MeSH terms:
Wounds and Injuries
Aspirin
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents