Evaluation of Dual Antithrombotic Therapy with Dabigatran and Ticagrelor in Acute Coronary Syndrome and Non-valvular Atrial Fibrillation Undergoing PCI
- Trial ID
- 2024-515056-20-00
- Protocol
- NBK182/1/2020
- Sponsor
- Medical University Of Gdansk
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **efficacy** of dual antithrombotic therapy with a reduced dose of **ticagrelor** plus standard-of-care **dabigatran** compared to triple therapy with **clopidogrel**, **aspirin**, and dabigatran in patients with **acute coronary syndrome** (ACS) and **non-valvular atrial fibrillation** (AF) undergoing **percutaneous coronary intervention** (PCI). The study aims to test the hypothesis that dual antithrombotic therapy is non-inferior in terms of bleeding risk and ischemic protection compared to the standard triple therapy. This is clinically relevant as it may offer a safer alternative with similar efficacy for patients requiring antithrombotic therapy post-PCI.
Participants
The clinical trial involves a study population comprising **male and female** patients aged between 18 and 99 years, diagnosed with **Acute Coronary Syndrome** (ACS) and non-valvular **Atrial Fibrillation** (AF) undergoing Percutaneous Coronary Intervention (PCI). The sponsor has not provided the total number of participants. The trial population includes individuals with new-onset or pre-existing non-valvular AF who have received at least two doses of dabigatran before randomization or were treatment-naïve prior to PCI. The AF may be paroxysmal, persistent, or permanent, provided it is not secondary to a reversible disorder unless long-term treatment with an oral anticoagulant is anticipated. Participants must have undergone a successful PCI within the previous 120 hours, with ACS presentations including ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina (UA). The study includes both genders and considers vulnerable populations, ensuring participants can provide informed consent according to ICH GCP guidelines and local regulations. Lifestyle factors such as diet, physical activity, or habits are not specified in the provided data.
Plans and Procedures
The clinical trial is designed to evaluate the safety and efficacy of dual antithrombotic therapy with a reduced dose of **ticagrelor** plus standard-of-care dabigatran compared to a triple therapy regimen consisting of clopidogrel, aspirin, and dabigatran in patients with acute coronary syndrome (ACS) and non-valvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). This study is a randomized, double-blind, controlled trial with an estimated duration from March 2021 to June 2026. Participants will be randomly assigned to either the study group or the control group to assess the primary endpoint, which is the occurrence of the first major or clinically relevant non-major bleeding event as defined by the International Society on Thrombosis and Haemostasis (ISTH). Secondary endpoints include a composite of thromboembolic events, such as myocardial infarction (MI), stroke, systemic embolism, or death, as well as unplanned revascularization procedures like PCI or coronary artery bypass grafting (CABG).
The trial will commence with an inclusion (screening) visit to confirm eligibility based on criteria such as age, presence of non-valvular AF, and recent successful PCI for ACS. Participants must be able to provide informed consent in accordance with ICH GCP guidelines. Following randomization, participants will undergo regular follow-up visits to monitor treatment adherence, assess safety outcomes, and collect data on efficacy endpoints. The end-of-study visit will conclude the trial, during which final assessments will be conducted to evaluate the long-term effects of the treatment regimens.
Participant involvement is expected to last up to 11 months, depending on the treatment group assignment. Conditions that may lead to early termination from the study include withdrawal of consent, occurrence of adverse events that necessitate discontinuation of the study medication, or any other medical condition that, in the opinion of the investigator, warrants removal from the trial for the safety of the participant. The trial is conducted in compliance with ethical standards and regulatory requirements to ensure the integrity of the data and the safety of the participants.
Treatment
The clinical trial involves the administration of **Brilique 60 mg film-coated tablets**, which contain the active substance **ticagrelor**. These tablets are manufactured by AstraZeneca AB and are classified as a chemical substance. The pharmaceutical form is a film-coated tablet, and the route of administration is oral. The maximum daily dose for this formulation is 120 mg, with a total maximum dose of 39,600 mg over the treatment period. The treatment duration for this formulation is up to 11 months. The tablets are labeled during the manufacturing process by an entity with the appropriate authorization and GMP certification, ensuring the integrity of the packaging is maintained. The investigational medicinal products (IMPs) are released for use in the clinical trial by a Qualified Person.
Additionally, the trial includes the use of **Brilique 90 mg film-coated tablets**, also containing **ticagrelor** as the active ingredient. This formulation is similarly produced by AstraZeneca AB and is administered orally in the form of film-coated tablets. The maximum daily dose for the 90 mg tablets is 180 mg, with a total maximum dose of 5,400 mg. The treatment period for this formulation is limited to 1 month. The labeling and release process for these tablets follows the same stringent procedures as the 60 mg tablets, ensuring compliance with regulatory standards.
In the study, the experimental treatment group receives a dual antithrombotic therapy consisting of a reduced dose of ticagrelor in combination with standard-of-care dabigatran. The control group is treated with a triple therapy regimen that includes clopidogrel, aspirin, and dabigatran. The primary objective of the trial is to evaluate the safety and efficacy of the dual therapy compared to the standard triple therapy in patients with acute coronary syndrome (ACS) and non-valvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).
Efficacy
Efficacy in the clinical trial titled "Dual Antithrombotic Therapy with Dabigatran and Ticagrelor in Patients with Acute Coronary Syndrome and Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention (ADONIS-PCI)" will be assessed by comparing two treatment regimens. The primary endpoint for evaluating efficacy is the occurrence of the first major or clinically relevant non-major bleeding event, as defined by the International Society on Thrombosis and Haemostasis (ISTH). Secondary endpoints include a composite of thromboembolic events such as myocardial infarction (MI), stroke, systemic embolism, or death, as well as unplanned revascularization procedures like percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).
The trial aims to test the hypothesis that dual antithrombotic therapy, which includes a reduced dose of **ticagrelor**, is non-inferior in terms of bleeding risk and ischemic protection compared to the standard triple therapy in patients with atrial fibrillation (AF) and after acute coronary syndrome (ACS), treated with PCI. The efficacy parameters will be collected and analyzed throughout the trial duration, with specific timepoints and methods not detailed in the provided data. The trial is designed as a confirmatory clinical trial, indicating its role in validating the efficacy and safety of the treatment regimens under investigation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and female patients aged 18-99 years
- Patients with new-onset or pre-existing non-valvular AF that have been receiving at least two doses of dabigatran before randomization or were treatment naïve prior to PCI. AF may be paroxysmal, persistent or permanent, but must not be secondary to a reversible disorder such as MI, pulmonary embolism, recent surgery, pericarditis or thyrotoxicosis unless long-term treatment with an OAC is anticipated.
- Patients presenting with ACS that had undergone a successful PCI (either drug-eluting stent (DES) implantation or plain old balloon angioplasty (POBA)) within the previous 120 hours (in case of the multistage PCI during primary hospitalization the time should be counted from the last stage). ACS may be ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina (UA).
- The patient must be able to give informed consent in accordance with ICH GCP guidelines and local legislation and/or regulations.
Exclusion Criteria
- Mechanical or biological heart valve prosthesis
- PCI with bare-metal stent implantation
- Unsuccessful PCI (>30% residual stenosis of the target lesion)
- Cardiogenic shock during current hospitalization
- Adverse bleeding or ischaemic event during current hospitalization
- Anaemia (haemoglobin <10 g/dL) or thrombocytopenia (platelet count <100 x109/L) at screening
- Severe renal impairment (creatinine clearance <30mL/min (estimated CrCl calculated by Cockcroft-Gault equation) at screening
- Active liver disease at screening defined as persistently elevated alanine aminotransferase (ALT) or aspartate transaminase (AST) levels >3 times the upper limit of normal (ULN)
- Use of fibrinolytic agents within 24 hours of screening
- Gastrointestinal bleeding within 1 month prior to screening unless, in the opinion of the Investigator, the cause has been permanently eliminated (e.g., by surgery)
- Major bleeding episode (reduction in the haemoglobin level of at least 2 g/dL, transfusion of at least two units of blood, or symptomatic bleeding in a critical area or organ), including life- threatening bleeding episode (symptomatic intracranial bleeding, bleeding with a decrease in the haemoglobin level of at least 5 g/dL or bleeding requiring transfusion of at least 4 units of blood or inotropic agents or necessitating surgery) within 1 month prior to screening
- Stroke within 1 month prior to screening
- Major surgery within 1 month prior to screening
- Malignancy or radiation therapy within 6 months prior to screening unless, in the opinion of the Investigator, the estimated life expectancy is greater than 36 months
- History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding unless the causative factor has been permanently eliminated or repaired
- Haemorrhagic disorder or bleeding diathesis (e.g. von Willebrand disease, haemophilia A or B or other hereditary bleeding disorder, history of spontaneous intra-articular bleeding, history of prolonged bleeding after surgery/intervention)
- Past an organ transplant or patient on the waiting list for organ transplant
- Need for continued treatment with systemic ketoconazole, itraconazole, posaconazole, cyclosporine, tacrolimus, dronedarone, rifampicin, phenytoin, carbamazepine, St. John’s Wort or any cytotoxic/myelosuppressive therapy
- Need for continued treatment with non-steroidal anti-inflammatory drugs (NSAIDs)
- Pre-menopausal women (last menstruation ≤1 year prior to screening) who: o Are pregnant or breastfeeding or o Are not surgically sterile or o Are of childbearing potential and not practicing two acceptable methods of birth control, or do not plan to continue practicing an acceptable method of birth control throughout the trial. Acceptable methods of birth control are oral or parenteral (patch, injection, implant) hormonal contraception, which has been used continuously for at least one month prior to the first dose of study medication, intrauterine device or intrauterine system, double-barrier method of contraception (condom and occlusive cap or condom and spermicidal agent), male sterilization and complete sexual abstinence (if acceptable by local authorities). Periodic abstinence is not an acceptable method of contraception
- Known allergy to dabigatran, ticagrelor, clopidogrel, aspirin
- Contraindications, in the Investigator’s opinion to dabigatran, ticagrelor, clopidogrel, or aspirin
- Participation in another trial with an investigational drug or device within the past 30 days preceding the screening visit (patients participating in an observational study only will not be excluded)
- Patients who are not willing or able to comply with the protocol requirements or considered unreliable by the Investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, who have a life expectancy less than the expected duration of the trial due to concomitant disease, or who have any condition which in the opinion of the Investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Not Recruiting | 01 Mar 2021 | 2230 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Brilique 60 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 120 | 11 | PRD3779152 |
Brilique 90 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 180 | 1 | PRD3534179 |