Ticagrelor for PCI Post Thrombolysis (SETFAST)

The Safety and Efficacy of Ticagrelor for Coronary Stenting Post Thrombolysis (SETFAST) Trial.

Ticagrelor is a first line therapy along with aspirin for patients undergoing primary PCI for STEMI. However, many patients are still treated with fibrinolytic therapy and the safety and efficacy of Ticagrelor has not been investigated in this patients population. The present study is proposed to study the safety and efficacy of Ticagrelor in patients undergoing PCI post fibrinolytic therapy for STEMI.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor

Detailed Description

The newer antiplatelet agents such as Ticagrelor have demonstrated superiority to Clopidogrel in patients presenting with acute coronary syndrome (ACS). At present Ticagrelor remains a first line therapy as an adjunct to aspirin for patients undergoing primary PCI for STEMI for reducing major adverse events. However, the safety and efficacy of Ticagrelor has not been investigated in patients with STEMI post fibrinolysis. Ticagrelor results in significantly higher platelet inhibition than aspirin or clopidogrel and may expose patients to an increased risk of bleeding if administered post thrombolysis. However, fibrinolytic therapy itself results in a prothrombotic milieu with greater activation of platelets, a condition that can be balanced with addition of stronger antiplatelet agents. Similar concerns were initially reflected for clopidogrel as an adjunct to fibrinolytic therapy but were later proven to be unsubstantiated. In fact, adjunct administration of clopidogrel to fibrinolytic therapy reduces major adverse events as shown by multiple studies and has become the standard of care recommended by guidelines. The present study is proposed to study the safety and efficacy of Ticagrelor in patients undergoing PCI post fibrinolytic therapy for STEMI.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Newmarket, Ontario, Canada, L3Y 2R2
      • Southlake Regional Health Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • Prairie Vascular Research Inc. (PVRI), Regina General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years and over.
2. Planned PCI between 4-24 hours after administration of fibrinolytic therapy for STEMI.
3. Treatment with aspirin and clopidogrel as an adjunct to fibrinolytic therapy.
4. Informed written consent.

Exclusion Criteria:

1. Atrial fibrillation or need for systemic anticoagulation therapy.
2. Prior PCI or coronary artery bypass grafting during past 3 months.
3. Active bleeding or high risk of bleeding based upon clinical assessment.
4. Known severe liver or renal disease or patient requiring dialysis.
5. Concomitant oral or IV therapy with strong cytochrome (CYP3A) inhibitors which cannot be stopped.
6. Contraindication to ticagrelor or clopidogrel.
7. Planned surgery during the study period.
8. Any of the following in the absence of a functioning implanted pacemaker: sick sinus syndrome, 2nd or 3rd degree AVB, documented syncope of suspected bradycardic origin.
9. Known clinically important thrombocytopenia or anemia.
10. Known pregnancy or lactation.
11. Condition which may either put the patient at risk or influence the result of the study.
12. Previous randomization in this SETFAST study.
13. Participation in another clinical study with an investigational product or device study over the past 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel arm; Clopidogrel 300 mg before PCI followed by 75 mg po OD	Drug: Clopidogrel; 300 mg bolus followed by 75 mg OD; Other Names: Plavix
Experimental: Ticagrelor arm; Ticagrelor 180 mg before PCI followed by 90 mg po BID	Drug: Ticagrelor; 180 mg bolus followed by 90 mg BID; Other Names: Brilinta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic platelet inhibition	Therapeutic platelet inhibition as determined by VerifyNow assay (PRU value <208) at 4±1 hours post PCI	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic platelet inhibition	Therapeutic platelet inhibition (PRU value <208) at 24±4 hours post PCI.	24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	MACE is a composite of death, re-infarction, stroke and bleeding	24 hours or discharge

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Prairie Vascular Research Inc.
• Investigators: Principal Investigator: Payam Dehghani, MD, Prairie Vascular Research Network, Regina, Saskatchewan; Principal Investigator: Asim Cheema, MD, St. Michael's Hospital, Toronto, Ontario

Publications and helpful links

General Publications

• Dehghani P, Lavoie A, Lavi S, Crawford JJ, Harenberg S, Zimmermann RH, Booker J, Kelly S, Cantor WJ, Mehta SR, Bagai A, Goodman SG, Cheema AN. Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI. Am Heart J. 2017 Oct;192:105-112. doi: 10.1016/j.ahj.2017.07.013. Epub 2017 Jul 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: August 22, 2013
• First Submitted That Met QC Criteria: August 22, 2013
• First Posted (Estimate): August 29, 2013

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: stenting; platelet activity; fibrinolytic therapy
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: 104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No