Anticoagulant Regimens Given to achieve thrombus regression and reduce clinical Outcomes among patients with Non device-related intra-cardiac thrombus: a randomized Assessment Under direct oral anticoagulant and vitamin K antagonist Therapy – the ARGONAUT trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

11 Apr 2023 → ongoing

Decision date (initial)

2024-05-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS / CHU DE NIMES

External identifiers

EU CT number

2024-512685-33-00

EudraCT number

2022-003335-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the impact of DOA in comparison to VKA (reference treatment) on net clinical benefit at 6 months among patients with intra-cardiac thrombus.

Secondary objectives 2

1. To evaluate at 6 and 12 months between patients treated with DOA or VKA the impact on: o All individual components of the composite primary endpoint o Cardiovascular death o All embolic complications (stroke, embolic myocardial infarction, peripheral artery occlusion, acute pulmonary embolism)
2. To evaluate at 6 and 12 months between patients treated with DOA or VKA the impact on total thrombus regression on cardiac imaging

Conditions and MedDRA coding

intra-cardiac thrombus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient with a non-device related intra-cardiac thrombus (all localizations in the four cavities) diagnosed by echocardiography, cardiac CT-scanner or cardiac magnetic resonance imaging independently of underlying heart disease.
2. Patient ≥18 years independently of sex or ethnic origin.
3. Anticoagulant naïve patient for at least 3 months
4. Patient affiliated to a health insurance program
5. Patient that accepted not to participate in other studies involving a study medication until the one-year follow-up visit. Registries and studies not involving a study drug are allowed.
6. Patient that signed the consent form

Exclusion criteria 16

1. Active internal bleeding or recent (< 6 months) major bleeding event requiring surgical procedure or transfusion
2. History of intracranial, intraocular, spinal bleeding or known intracranial neoplasm, arteriovenous malformation, or aneurysm
3. Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months
4. Planned invasive procedure with potential for uncontrolled bleeding
5. Impaired hemostasis such as known International Normalized Ratio (INR) >1.5, past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand’s disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count <100,000/μL)
6. Severe chronic renal failure (creatinine clearance<30ml/min)
7. Known significant liver disease or ALT >3x the ULN
8. Device related thrombus (mechanical valve prosthesis, left atrial appendage or septal closure devices, pacemaker leads)
9. Patients with mechanical valve prosthesis
10. Cardiogenic shock
11. Pregnancy or breast-feeding patient
12. Known allergy or hypersensitivity to VKA or DOA drugs
13. Inability or unwillingness to comply with study-related procedures
14. Participation in another clinical research protocol with other investigational agents or devices within the previous 30 days, planned use of investigational drugs or devices, or previous enrolment in this trial (participation in a trial of routine care is authorized at the same time)
15. Patient under tutorship or curatorship
16. Contra-indications mentioned for in SCP (Summary of product characteristics)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Net clinical benefit endpoint at 6 months: composite endpoint of all-cause death, myocardial infarction, stroke, acute peripheral emboli, acute pulmonary embolism, thrombus persistence and clinically relevant bleedings (Bleeding Academic Research Consortium 2, 3 and 5).

Secondary endpoints 2

1. - Secondary efficacy endpoints: o All individual components of the composite ischemic endpoint at 6 and 12 months o Systemic embolism defined by the composite of stroke, embolic myocardial infarction, peripheral artery occlusion and acute pulmonary embolism at 6 and 12 months o Cardiovascular death at 6 and 12 months o Total thrombus regression at 6 and 12 months o Thrombus recurrence at different cardiac imaging follow-up
2. - Secondary safety endpoints: o Clinically relevant bleedings (international Bleeding Academic Research Consortium (BARC) types 2 to 5) at 6 and 12 months o Major bleedings (BARC 3 to 5) at 6 and 12 months

Investigational products

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

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

Place Du Professeur Robert Debre

City

Nimes

Postcode

30900

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

leonie gazel

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

leonie gazel

Locations

1 EU/EEA country · 1 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 21 files

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

Application history

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