Dual Antithrombotic Therapy with Dabigatran and Ticagrelor in Patients with Acute Coronary Syndrome and Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention (ADONIS-PCI)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

31 Jul 2021 → 31 Oct 2025

Decision date (initial)

2024-11-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency (Agencja Badań Medycznych)

External identifiers

EU CT number

2024-515056-20-00

EudraCT number

2020-004887-24

ClinicalTrials.gov

NCT04695106

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To compare the safety and efficacy of two types of treatment: dual antithrombotic therapy with reduced dose of ticagrelor plus standard-of-care dabigatran (study group) and triple therapy with clopidogrel plus aspirin plus dabigatran (control group) in patients with AF and ACS, treated with PCI. The primary objective of this study is to test the hypothesis that dual antithrombotic therapy, including reduced dose ticagrelor, is non-inferior regarding bleeding risk and ischaemic protection compared to the standard triple therapy in patients with AF and after ACS, treated with PCI.

Secondary objectives 1

1. Not applicable

Conditions and MedDRA coding

Acute Coronary Syndrome and Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. Male and female patients aged 18-99 years
2. 2. 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.
3. 3. 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).
4. 4. The patient must be able to give informed consent in accordance with ICH GCP guidelines and local legislation and/or regulations.

Exclusion criteria 24

1. Mechanical or biological heart valve prosthesis
2. PCI with bare-metal stent implantation
3. Unsuccessful PCI (>30% residual stenosis of the target lesion)
4. Cardiogenic shock during current hospitalization
5. Adverse bleeding or ischaemic event during current hospitalization
6. Anaemia (haemoglobin <10 g/dL) or thrombocytopenia (platelet count <100 x109/L) at screening
7. Severe renal impairment (creatinine clearance <30mL/min (estimated CrCl calculated by Cockcroft-Gault equation) at screening
8. 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)
9. Use of fibrinolytic agents within 24 hours of screening
10. 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)
11. 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
12. Stroke within 1 month prior to screening
13. Major surgery within 1 month prior to screening
14. 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
15. History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding unless the causative factor has been permanently eliminated or repaired
16. 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)
17. Past an organ transplant or patient on the waiting list for organ transplant
18. Need for continued treatment with systemic ketoconazole, itraconazole, posaconazole, cyclosporine, tacrolimus, dronedarone, rifampicin, phenytoin, carbamazepine, St. John’s Wort or any cytotoxic/myelosuppressive therapy
19. Need for continued treatment with non-steroidal anti-inflammatory drugs (NSAIDs)
20. 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
21. Known allergy to dabigatran, ticagrelor, clopidogrel, aspirin
22. Contraindications, in the Investigator’s opinion to dabigatran, ticagrelor, clopidogrel, or aspirin
23. 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)
24. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. First major or clinically relevant non-major bleeding event (ISTH)

Secondary endpoints 1

1. Composite of thromboembolic events (MI, stroke, systemic embolism) or death or unplanned revascularization (PCI or CABG)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Chief Medical Officer; Principal Investigator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Director of the Clinical Research Support Centre

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications