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
Overview
- Phase
- Phase 4
- Intervention
- ticagrelor
- Conditions
- Myocardial Injury
- Sponsor
- The Cleveland Clinic
- Enrollment
- 6
- Locations
- 24
- Primary Endpoint
- Major Adverse Cardiovascular Events
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
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.
Investigators
Venu Menon
MD, FACC, FAHA, Director CICU, CEC-C5, Fellowship Program Cardiovascular Imaging
The Cleveland Clinic
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.
Arms & Interventions
ticagrelor
ticagrelor 90mg bid
Intervention: ticagrelor
aspirin
Patients in the aspirin arm will receive aspirin 81 mg daily orally
Intervention: aspirin
Outcomes
Primary Outcomes
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 Outcomes
- Cardiovascular Death(Up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.)
- Non-fatal Myocardial Infarction or Coronary Revascularization(up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.)
- All-cause Death(up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.)
- Non-fatal Stroke(up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.)