Myocardial Injury
Conditions
Keywords
ticagrelor, non-cardiac surgery, elevated troponin, myocardial injury
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.
Interventions
DRUGticagrelor
ticagrelor 90 mg bid
DRUGaspirin
aspirin 81 mg daily
Sponsors
AstraZeneca
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiovascular Events | 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
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular Death | 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 | 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 | 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 | 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
| Measure | Time frame |
|---|---|
| The Number of Participants With Bleeding According to Bleeding Academic Research Consortium (BARC) Definitions | up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor ticagrelor 90mg bid
ticagrelor: ticagrelor 90 mg bid | 1 |
| Aspirin Patients in the aspirin arm will receive aspirin 81 mg daily orally
aspirin: aspirin 81 mg daily | 5 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Early study termination | 1 | 5 |
Baseline characteristics
| Characteristic | Ticagrelor | Aspirin | Total |
|---|---|---|---|
| Age, Customized > or = to 40 years | 1 Participants | 5 Participants | 6 Participants |
| Region of Enrollment United States | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 5 |
| other Total, other adverse events | 0 / 1 | 0 / 5 |
| serious Total, serious adverse events | 0 / 1 | 0 / 5 |
Outcome results
Primary
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.
Time frame: up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Major Adverse Cardiovascular Events | 0 Participants |
| Aspirin | Major Adverse Cardiovascular Events | 0 Participants |
Secondary
All-cause Death
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | All-cause Death | 0 Participants |
| Aspirin | All-cause Death | 0 Participants |
Secondary
Cardiovascular Death
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Cardiovascular Death | 0 Participants |
| Aspirin | Cardiovascular Death | 0 Participants |
Secondary
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.
Time frame: up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Non-fatal Myocardial Infarction or Coronary Revascularization | 0 Participants |
| Aspirin | Non-fatal Myocardial Infarction or Coronary Revascularization | 0 Participants |
Secondary
Non-fatal Stroke
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Non-fatal Stroke | 0 Participants |
| Aspirin | Non-fatal Stroke | 0 Participants |
Other Pre-specified
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | The Number of Participants With Bleeding According to Bleeding Academic Research Consortium (BARC) Definitions | 0 Participants |
| Aspirin | The Number of Participants With Bleeding According to Bleeding Academic Research Consortium (BARC) Definitions | 0 Participants |