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

Myocardial Injury Clinical Trial

— INTREPID  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02291419
• Other study ID #: CCAZ-2014
• Status: Terminated
• Phase: Phase 4
• First received: November 5, 2014
• Last updated: February 8, 2017
• Start date: July 2015
• Est. completion date: June 2016

Study information

• Verified date: February 2017
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myocardial Injury
• Wounds and Injuries

Intervention

Drug:
• ticagrelor
ticagrelor 90 mg bid
• aspirin
aspirin 81 mg daily

Locations

Country	Name	City	State
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	McLaren Bay Region	Bay City	Michigan
United States	Overlake Hospital Medical Center	Bellevue	Washington
United States	Cincinnati VA Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	VA Medical Center - Cleveland Louis Stokes	Cleveland	Ohio
United States	VA North Texas Health Care System	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Saint Vincent Medical Group	Indianapolis	Indiana
United States	University of Florida College of Medicine - Jacksonville	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Arkansas Site Management Service, LLC	Little Rock	Arkansas
United States	Central Georgia Heart Center	Macon	Georgia
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of South Alabama Health System	Mobile	Alabama
United States	McLaren Macomb	Mount Clemens	Michigan
United States	New York University School of Medicine	New York	New York
United States	Florida Hospital Orthopaedic Institute and Fracture Care Center	Orlando	Florida
United States	Oregon Health and Science University	Portland	Oregon
United States	University of South Florida	Tampa	Florida
United States	Oklahoma Heart Institute	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	AstraZeneca

Country where clinical trial is conducted

United States, 

References & Publications (3)

POISE Study Group., Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Málaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. doi: 10.1016/S0140-6736(08)60601-7. — View Citation

Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators., Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012 Jun 6;307(21):2295-304. doi: 10.1001/jama.2012.5502. Erratum in: JAMA. 2012 Jun 27;307(24):2590. — View Citation

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators., Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
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.	up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Secondary	Cardiovascular Death	Time to first occurence of Cardiovascular death. The number of patients with events was reported.	Up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
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.	up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Secondary	All-cause Death	Time to first occurence of All-cause death. The number of participants with events was reported.	up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.
Secondary	Non-fatal Stroke	Time to first occurence of Non-fatal stroke. The number of participants with events was reported.	up to 6 months. The planned duration of treatment was one year but the study was terminated after 6 months.