Clinical trial NCT06667349: TISSARA Trial: Ticagrelor Intervention to Reduce Stent Thrombosis and Acute MI Risk
Official title: Ticagrelor Intervention to Suppress Stent Thrombosis and Acute MI Risk (TISSARA) Trial: An LMIC Health System Initiative in the World's Busiest Primary PCI Center
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: STEMI - ST Elevation Myocardial Infarction
Stent Thrombosis
Antiplatelet Agents
Keywords: clinical trial
STEMI
stent thrombosis
ticagrelor
clopidogrel
health care intervention
Lead sponsor: National Institute of Cardiovascular Diseases, Pakistan
Sponsor class: OTHER
First posted: 2024-10-31
Enrollment: 1727
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1727
Primary purpose: PREVENTION

Brief summary: Stent thrombosis (ST) remains a critical complication following primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI). At the National Institute of Cardiovascular Diseases in Karachi-recognized as the world's busiest PPCI center-reported rates of ST range from 4% to 6%. In response to this pressing issue, the health system has implemented a new two-week post-PCI regimen featuring ticagrelor, aimed at enhancing patient outcomes and reducing the risk of stent-related complications.

The TISSARA Trial is designed to rigorously assess the effectiveness of this intervention on cardiovascular outcomes in STEMI patients.

Between August, 2023 and March 2024, a total of 1,773 patients were enrolled in the trial, with 970 patients discharged on Tissara (Ticagrelor) (Ferozsons laboratories Ltd, Lahore, Pakistan) (TG) and 803 patients receiving clopidogrel (CG) following their primary PCI procedures. Each group was carefully monitored for a duration of three months to evaluate the incidence of stent thrombosis and other relevant cardiovascular events. The primary endpoint of this trial is the occurrence of stent thrombosis within the follow-up period, providing critical insights into the safety and efficacy of the ticagrelor regimen in this high-risk population.

This comprehensive approach aims to contribute valuable data that may influence future treatment protocols and improve the standard of care for patients undergoing PCI in similar healthcare settings.

Detailed description: The TISSARA Trial aims to compare the incidence rates of stent thrombosis (ST) and major adverse cardiovascular events (MACE) among patients receiving ticagrelor therapy versus those treated with conventional clopidogrel therapy following primary percutaneous coronary intervention (PPCI) f or ST elevation myocardial infarction at NICVD, Karachi, Pakistan.

Study Cohorts:

* Ticagrelor Cohort: Comprises consecutive patients receiving ticagrelor as part of the dual antiplatelet therapy (DAPT) regimen mandated for a minimum of two weeks post PPCI.
* Clopidogrel Cohort: Included patients who received clopidogrel as part of the conventional DAPT protocol.

Selection Criteria:

• All consecutive patients presenting with ST-elevation myocardial infarction (STEMI) and undergoing primary PCI with drug-eluting stents (DES).

Exclusion Criteria:

* Patients who underwent plain old balloon angioplasty (POBA) or left heart catheterization (LHC) only.
* Patients who declined to provide consent.
* Patient with high bleeding risk
* Prior history of IC hemorrhage
* Prior CVA within past one year
* On oral anticoagulant Study Variables and Operational Definitions
* ST-Elevation Myocardial Infarction (STEMI): Diagnosis based on at least two of the following criteria:

  * Typical chest pain lasting more than 20 minutes, characterized by retrosternal pain radiating to the left arm or shoulder, worsening with exertion or emotional stress, and alleviated by rest or nitroglycerin.
  * New ST elevation in at least two contiguous leads: greater than 2 mm in men or greater than 1 mm in women in leads V2 to V3, and/or greater than 1 mm in other contiguous chest leads or limb leads.
* Primary PCI: The strategy of directly taking a STEMI patient to the cardiac catheterization laboratory for mechanical revascularization via balloon angioplasty and coronary stenting.
* Stent Thrombosis:

  * Definite Stent Thrombosis: Confirmed by angiographic or pathological evidence of partial or total thrombotic occlusion within the peri-stent area, along with acute ischemic symptoms, ischemic ECG changes, or elevated cardiac biomarkers.
  * Probable Stent Thrombosis: Unexplained death within 30 days of stent implantation or myocardial infarction related to documented acute ischemia in the stented territory, without angiographic confirmation of stent thrombosis.
  * Possible Stent Thrombosis: Unexplained death occurring beyond 30 days.
  * Early Stent Thrombosis: Occurs within 24 hours post-PCI.
  * Subacute Stent Thrombosis: Occurs from 24 hours to 30 days post-PCI.
* Major Adverse Cardiovascular Events (MACE): Defined as a composite of:

  * All-cause mortality
  * Cardiovascular mortality
  * Myocardial infarction (with or without revascularization)
  * Unplanned hospitalization due to heart failure
  * Stroke or cerebrovascular events Data Collection Procedure The study was conducted after receiving approval from the ethical review committee of NICVD, Karachi. Verbal informed consent was obtained from all participants, ensuring confidentiality. Patients presenting with STEMI who underwent primary PCI with second-generation DES were included. Data on demographic characteristics, financial status, treatment compliance, complications, hospitalizations, and emergency room visits were collected using a structured questionnaire. The collected data were securely stored and accessible to the primary investigators and co-investigators. Patients were followed up at 15 days and one month in the outpatient clinic to assess medication compliance, side effects, and bleeding.

Eligibility criteria: Inclusion Criteria: consecutive patients presenting with ST-elevation myocardial infarction (STEMI) and undergoing primary PCI with drug-eluting stents (DES).

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Exclusion Criteria:

* Patients who underwent plain old balloon angioplasty (POBA) or left heart catheterization (LHC) only.

  * Patients who declined to provide consent.
  * Patient with high bleeding risk
  * Prior history of IC hemorrhage
  * Prior CVA within past one year
  * On oral anticoagulant

Primary outcomes:
measure: Stent Thrombosis
timeFrame: Stent thrombosis occurring 24 hours to 30 DAYS
Secondary outcomes:
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: National Institute of Cardiovascular Diseases
state: Sindh
Study officials:
affiliation: National Institute of Cardiovascular Diseases
name: Abdul Hakeem, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kumar R, Ammar A, Saghir T, Sial JA, Shah JA, Kumar A, Shaikh AH, Achakzai AS, Qamar N, Karim M. Incidence, Predictors, and Outcomes of Acute and Sub-acute Stent Thrombosis after Emergency Percutaneous Coronary Revascularization with Drug-Eluting Stents: A Prospective Observational Study. Glob Heart. 2022 Mar 30;17(1):24. doi: 10.5334/gh.1112. eCollection 2022.
citation: Schulz S, Schuster T, Mehilli J, Byrne RA, Ellert J, Massberg S, Goedel J, Bruskina O, Ulm K, Schomig A, Kastrati A. Stent thrombosis after drug-eluting stent implantation: incidence, timing, and relation to discontinuation of clopidogrel therapy over a 4-year period. Eur Heart J. 2009 Nov;30(22):2714-21. doi: 10.1093/eurheartj/ehp275. Epub 2009 Jul 11.
citation: Dubey G, Verma SK, Bahl VK. Primary percutaneous coronary intervention for acute ST elevation myocardial infarction: Outcomes and determinants of outcomes: A tertiary care center study from North India. Indian Heart J. 2017 May-Jun;69(3):294-298. doi: 10.1016/j.ihj.2016.11.322. Epub 2016 Nov 30.