Rationale and design of the TADCLOT trial: A double blind randomized controlled trial comparing twice a day clopidogrel vs ticagrelor in reducing major cardiac events in patients with acute STEMI undergoing primary percutaneous coronary intervention

Abstract

Background: Ticagrelor has been proven superior to clopidogrel in reducing adverse cardiovascular events in patients with acute coronary syndrome (ACS), yet economic factors often favor clopidogrel in real-world clinical practice. Although double dose clopidogrel has shown potential benefits over once-daily regimens, its direct comparison with ticagrelor in ST-elevation myocardial infarction (STEMI) patients remains unexplored.

Methods and design: Twice a Day Clopidogrel vs. Ticagrelor in Reducing Major Cardiac Events in Patients with Acute STEMI Undergoing Primary PCI (TADCLOT) trial is a double-blind, randomized controlled trial conducted at the National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan. It is designed as a superiority trial to evaluate the efficacy and safety of ticagrelor over twice-daily clopidogrel in reducing major adverse cardiac events (MACE) in STEMI patients undergoing primary percutaneous coronary intervention (PCI). Following successful PCI for STEMI, and when the patient is deemed suitable for discharge, patients are randomized 1:1 to receive either ticagrelor (180 mg loading dose followed by 90 mg BID for 30 days) or clopidogrel (600 mg loading dose followed by 75 mg BID for 30 days). The primary endpoint is the rate of major adverse cardiac events (MACE), a composite of death, myocardial infarction, stent thrombosis, target lesion revascularization, or stroke at 30 days following randomization. Secondary endpoints include the individual components of MACE, bleeding complications, and drug discontinuation due to adverse events. Enrollment has reached 88%, with 2,200 patients planned to complete the trial.

Implications: The TADCLOT trial will provide crucial insights into the comparative efficacy of ticagrelor versus twice-daily clopidogrel in reducing early stent thrombosis and improving outcomes in STEMI patients undergoing primary PCI. The trial will particularly contribute valuable insights for post-PCI care, considering both the economic and genetic context of the high risk South Asian population.

Trial registration: ClinicalTrials.gov NCT06318481.