Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation Compared to Medical Therapy (CLOSURE-AF)

Charité University Medicine Berlin

Status and phase

Completed

Phase 4

Conditions

Atrial Fibrillation

Treatments

Drug: Warfarin

Drug: Edoxaban

Drug: Rivaroxaban

Device: CE-mark approved LAA closure devices

Drug: Dabigatran

Drug: Apixaban

Drug: Clopidogrel

Drug: Acetylsalicylic acid

Drug: Phenprocoumon

Study type

Interventional

Funder types

Other

Identifiers

NCT03463317

CLOSURE-AF-DZHK16

Details and patient eligibility

About

The study goal is to determine the clinical benefit of percutaneous catheter-based left atrial appendage (LAA) closure in patients with non-valvular atrial fibrillation (NVAF) at high risk of stroke (CHA2DS2-VASc Score ≥2) as well as high risk of bleeding as compared to best medical care (including a [non-vitamin K] oral anticoagulant [(N)OAC] when eligible).

Full description

The individualized therapy with oral anticoagulants is considered to be an essential preventive therapy in patients with atrial fibrillation. The risk of stroke can be reduced by approximately 65%. However, long-term anticoagulation therapy also increases the risk of major bleeding.

A significant proportion of patients at high risk of stroke do not tolerate long-term anticoagulation due to various relative or absolute contraindications. As demonstrated in previous studies with non-vitamin K antagonist anticoagulants (NOAK), 20-25% of patients were unable to tolerate long-term anticoagulation therapy.

For this reason, additional therapeutic approaches for stroke prevention in patients with atrial fibrillation have been developed.

A promising approach is catheter-based closure of the left atrial appendage, because more than 90% of cardiac thrombi in patients with non-valvular atrial fibrillation are detected in the left atrial appendage. Recent registry studies show that the safety of LAA occluder implantation is promising. However, further scientific studies are required, in order to explore more benefits of the underlying method and eligible patients for implantation.

Study objectives:

Enrollment

912 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed written informed consent
Documented atrial fibrillation (paroxysmal, persistent, long-standing persistent or permanent)
CHA2DS2VASc-Score ≥2
High risk of bleeding under oral anticoagulation or contraindication for (N)OAC therapy, in particular patients with at least one of the following conditions:
- HAS-BLED-Score ≥3
- Prior intracranial/intraspinal bleed, intraocular bleed compromising vision (BARC: type 3c)
- Hemorrhagic/bleeding complication fulfilling BARC type 3a or 3b: gastrointestinal tract, genitourinary tract or respiratory tract bleeding, where the patient is considered to be at a persistently increased risk of bleeding, e.g. the cause of bleeding cannot be successfully eliminated
- Chronic kidney disease with eGFR 15-29 ml/min/1.73 m2
- Any recurrent bleeding making chronic anticoagulation not feasible
Subject eligible for an LAA occluder device
Age ≥18 years
Willing and capable of providing informed consent, participating in all associated study activities
negative SARS-CoV-2 PCR test (no longer than 48 hours prior to randomization in outpatients or not older than 14 days in continuously hospitalized patients without signs of COVID-19 infection) or negative SARS- CoV-2 rapid antigen test (no longer than 24 hours prior to randomization)

Exclusion criteria

Absolute contraindication to acetylsalicylic acid
Comorbidities other than AF requiring chronic (N)OAC therapy, e.g. mechanical heart valve prosthesis
Symptomatic carotid disease (if not treated)
Complex aortic atheroma with mobile plaque (Kronzon classification grade V)
Heart transplant
Active infection or symptoms suggestive of COVID-19 infection or active endocarditis or other infections resulting in bacteremia
Cardiac tumor
Severe liver failure (Child-Pugh class C or liver failure with coagulopathy)
Severe renal failure (GFR <15 ml/min/1.73m2 or current requirement for dialysis defined as current, regular renal replacement therapy performed at least weekly including hemodialysis and peritoneal dialysis within the last 30 days)
Pregnancy or breastfeeding
For female patients of reproductive potential: Unwilling to agree to use a highly effective method of contraception (Pearl index <1) throughout the study period
Subject with participation in another interventional clinical trial during this study or within 30 days before entry into this trial.
Known terminating disease with life expectancy <1 year (including those with end-stage heart failure)
Subjects, who are committed to an institution due to binding official or court order
Subject who is dependent on the Site, the Site Investigator, any sub- investigator, his/her representative and/or the sponsor
Persons who are not proficient in the German language
Unstable/not fully recompensated acute heart failure corresponding to NYHA class III and/or IV
Subjects with known antiphospholipid syndrome
Subjects with planned cardiac or non-cardiac surgery or intervention. (These subject can be included 30 days after such intervention / surgery.)

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

912 participants in 2 patient groups

LAA closure group

Experimental group

Description:

Left atrial appendage closure by use of CE-mark approved LAA closure devices followed by post procedure treatment (antiplatelet therapy e.g. acetylsalicylic acid, clopidogrel)

Treatment: