Apixaban vs Dual Antiplatet Therapy Study After Left Atrial Appendage Occlosure (ADALA)

NCT05632445 | Completed Phase 4 DMC

• 1 other identifier: CV 185-685
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To demonstrate superiority of a strategy of anticoagulation with apixaban 5mg/2.5mg bid as compared with the current standard of care (dual antiplatelet therapy) after occlusion of the left atrial appendage (LAAC) in patients with atrial fibrillation (AF). Rationale: Data on antithrombotic therapy after LAAC are scarce and no randomized evaluation has been performed to demonstrate what is the best antithrombotic strategy. LAAO in patients without contraindication to chronic anticoagulants (PROTECT-AF regimen) is a 6-week period of anticoagulation with warfarin associated with aspirin, followed by once daily clopidogrel (75 mg) and aspirin (81-325 mg) until the 6 months visit, then aspirin alone is continued indefinitely, as tested in the pivotal trials. LAAO is also being used as an alternative to warfarin anticoagulation when patients have a contraindication or are unsuitable to warfarin. These patients usually receive a regimen of daily clopidogrel and aspirin (DAPT) for 3 months. Some may receive a shorter duration of DAPT or even only single antiplatelet therapy (SAPT) in case of excess bleeding risk. This antiplatelet regimen has never been compared with any anticoagulation regimen after LAAC. The Investigators propose to evaluate a unique antithrombotic strategy after LAAC for atrial fibrillation, whatever the indication of LAAC, including patients not suitable for long term warfarin anticoagulation. This strategy uses apixaban 5mg (with dose adjustment when necessary) which will be compared to the standard of care based on antiplatelet therapy and which may vary according to the risk profile of the patient. Apixaban, has demonstrated a mortality benefit associated with significant reductions in stroke, systemic embolism and major bleeding versus VKA. In addition, apixaban is the only NOAC which has demonstrated superiority over aspirin alone, in AF patients not suitable for chronic warfarin anticoagulation, to prevent cardio-embolic events with a safety profile similar to aspirin.The Investigators therefore formulate the hypothesis that apixaban is superior to standard of care (APT) to prevent cardiovascular events and bleeding complications after LAAO. Population: Inclusion criteria: AF patients who have undergone a successful LAAO procedure. Exclusion criteria include any indication for triple antithrombotic treatment, mechanical heart valve, use of prasugrel or ticagrelor, serious renal failure defined as a creatinine clearance \<15mL/min, contraindication to any form of anticoagulation or antiplatelet therapy. Randomization will occur always before hospital discharge as soon as the patient is stable or stabilized after the procedure. Randomization: Apixaban vs. APT, both for 3 months. Groups: 1/Apixaban 5mg or 2.5mg bid (if dose adjustment needed). 2/ DAPT using low-dose ASA (75-100mg) and clopidogrel (75mg); or in patients with a history of intracranial hemorrhage (ICH) SAPT (aspirin or clopidogrel) will be used instead of DAPT from the time of randomization. Follow-up: 12 months from randomization Primary endpoint: combined enpoint of death, MI, stroke, thromboembolic complications, major or significant bleeding at 3 months follow-up. Sample size: In order to find a 16% difference in the event rates among the two treatment strategies, using a logrank test with a 5% two-sided significance level, we will need 76 patients in each group (152 in total). However, to compensate patient drop out, a total of 160 patients will be included in the study. Recruitment : 24 months Centers: 3 centers in Spain.

Conditions

Left Atrial Appendage Occlusion

Keywords

Left atrial appendage occlusion, atrial fibrillation

Outcome Measures

Primary Outcomes (1)

• Combined Safety-Efficacy at 3 months Apixaban vs dual antiplatelet therapy

  Combined of efficacy (thromboembolic events prevention and device thrombosis) and safety (major bleeding incidence) at 3 months with both strategies.

  3 months

Secondary Outcomes (1)

• Combined Safety-Efficacy at 12 months apixaban vs dual antiplatelet therapy

  12 months

Study Arms (2)

Apixaban

OTHER

Apixaban 5mg bid oral.Duration: 3 months Aspirin 80 / 100 mg bid oral. Duration: 9 months

Drug: Apixaban vs. DAPT

DAPT

OTHER

Aspirin 80/100 mg + Clopidogrel 75 mg bid oral. Duration: 3 months Aspirin 80 / 100 mg bid oral. Durtaion: 9 months

Drug: Apixaban vs. DAPT

Interventions

Apixaban vs. DAPT DRUG

Apixaban vs DAPT after LAAO

Apixaban; DAPT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• NVAF (paroxysmal, persistent or permanent)
• CHADS2 score \>1 or CHA2DS2-VASc score \>2
• Adequate anatomy for LAA closure and contraindication for OAC (absolute or relative).
• Able to give informed consent and to be followed -up (phone and clinical visit)

You may not qualify if:

• Patients with mechanical prostheses, evidence of thrombus, complex aortic atheroma or symptomatic carotid disease.
• Contraindication for TEE studies
• Platelets \<40000
• Absolute contraindication to Apixaban for 3 months (severee renal failure with CI creat \<15 ml/h or severe liver disease Child B or C) or allergy to the drug.
• Contraindication to any form of anticoagulation or antiplatelet therapy.
• Patients with a history of drug or alchol abuse, or psychosocial reasons that preclude the follow-up of the patient
• Women of childbearing potential (WOCB)

Sponsors & Collaborators

• DR. XAVIER FREIXA: lead

Study Sites (1)

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Related Publications (24)

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  PMID: 19717844 RESULT

• Freixa X, Cruz-Gonzalez I, Cepas-Guillen P, Millan X, Antunez-Muinos P, Flores-Umanzor E, Asmarats L, Regueiro A, Lopez-Tejero S, Li CP, Sanchis L, Rodes-Cabau J, Arzamendi D. Low-Dose Direct Oral Anticoagulation vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion: The ADALA Randomized Clinical Trial. JAMA Cardiol. 2024 Oct 1;9(10):922-926. doi: 10.1001/jamacardio.2024.2335.

  PMID: 39110427 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dabit Arzamendi, Md, PhD

  Hospital Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD; PhD. Interventional Cardiologist. Principal Investigator

Study Record Dates

• First Submitted: August 5, 2022
• First Posted: November 30, 2022
• Study Start: May 1, 2019
• Primary Completion: June 12, 2019
• Study Completion: October 30, 2022
• Last Updated: November 30, 2022

Record last verified: 2022-11

Locations

ES (1)