Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery
Condition: Myocardial Injury
MeSH terms: Wounds and Injuries
Intervention: ticagrelor; aspirin
Intervention description: ticagrelor 90 mg bid; aspirin 81 mg daily
Intervention MeSH terms: Aspirin; Ticagrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: ticagrelor; non-cardiac surgery; elevated troponin; myocardial injury

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.
    

Eligibility 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.