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

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ClinicalTrials.gov Identifier: NCT02291419
Recruitment Status : Terminated (Enrollment expectations were not met)
First Posted : November 14, 2014
Results First Posted : February 9, 2017
Last Update Posted : February 9, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Venu Menon, The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE November 5, 2014
First Posted Date  ICMJE November 14, 2014
Results First Submitted Date  ICMJE February 8, 2017
Results First Posted Date  ICMJE February 9, 2017
Last Update Posted Date February 9, 2017
Study Start Date  ICMJE July 2015
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2014)
Major Adverse Cardiovascular Events [ Time Frame: one year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2014)
  • Death from cardiovascular causes [ Time Frame: one year ]
  • Non-fatal Myocardial Infarction or Coronary Revascularization [ Time Frame: one year ]
    PCI, CABG
  • All-cause Death [ Time Frame: one year ]
  • Non-fatal Stroke [ Time Frame: one year ]
Current Other Pre-specified Outcome Measures
 (submitted: February 8, 2017)
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. ]
Original Other Pre-specified Outcome Measures
 (submitted: November 13, 2014)
Bleeding according to Bleeding Academic Research Consortium (BARC) definitions [ Time Frame: one year ]
 
Descriptive Information
Brief Title  ICMJE Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Myocardial Injury
Intervention  ICMJE
  • Drug: ticagrelor
    ticagrelor 90 mg bid
    Other Name: Brilinta
  • Drug: aspirin
    aspirin 81 mg daily
    Other Name: Bayer, ASA
Study Arms  ICMJE
  • Experimental: ticagrelor
    ticagrelor 90mg bid
    Intervention: Drug: ticagrelor
  • Active Comparator: aspirin
    Patients in the aspirin arm will receive aspirin 81 mg daily orally
    Intervention: Drug: aspirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 7, 2016)
6
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2014)
1000
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02291419
Other Study ID Numbers  ICMJE CCAZ-2014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Venu Menon, The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Venu Menon, MD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP