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

Phase 4

Terminated

• Conditions: Myocardial Injury
• Interventions: Drug: ticagrelor; Drug: aspirin

• Registration Number: NCT02291419
• Lead Sponsor: The Cleveland Clinic

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 Timeline

• Study First Submitted: 2014-11-05
• Study First Submitted QC: 2014-11-13
• Study First Posted: 2014-11-14
• Study Start: 2015-07
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Status Verified: 2017-02
• Results First Submitted: 2017-02-08
• Results First Submitted QC: 2017-02-08
• Last Update Submitted: 2017-02-08
• Results First Posted: 2017-02-09
• Last Update Posted: 2017-02-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ticagrelor	ticagrelor	ticagrelor 90mg bid
aspirin	aspirin	Patients in the aspirin arm will receive aspirin 81 mg daily orally

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (24)

University of South Florida; 🇺🇸 Tampa, Florida, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

VA North Texas Health Care System; 🇺🇸 Dallas, Texas, United States

University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

Cincinnati VA Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of South Alabama Health System; 🇺🇸 Mobile, Alabama, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Oklahoma Heart Institute; 🇺🇸 Tulsa, Oklahoma, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

University of Florida College of Medicine - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Florida Hospital Orthopaedic Institute and Fracture Care Center; 🇺🇸 Orlando, Florida, United States

Arkansas Site Management Service, LLC; 🇺🇸 Little Rock, Arkansas, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Saint Vincent Medical Group; 🇺🇸 Indianapolis, Indiana, United States

Sinai Hospital of Baltimore; 🇺🇸 Baltimore, Maryland, United States

McLaren Bay Region; 🇺🇸 Bay City, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

McLaren Macomb; 🇺🇸 Mount Clemens, Michigan, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

New York University School of Medicine; 🇺🇸 New York, New York, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Overlake Hospital Medical Center; 🇺🇸 Bellevue, Washington, United States

Central Georgia Heart Center; 🇺🇸 Macon, Georgia, United States

VA Medical Center - Cleveland Louis Stokes; 🇺🇸 Cleveland, Ohio, United States