Left Atrial Appendage Occlusion Versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation

Stroke Clinical Trial

— Occlusion-AF  

Official title:

Left Atrial Appendage Occlusion Versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation. A Multicenter Randomized Clinical Trial. (Occlusion-AF)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03642509
• Other study ID #: Occlusion-AF-AUH250418-32
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2019
• Est. completion date: October 1, 2030

Study information

• Verified date: December 2023
• Source: University of Aarhus
• Contact: Kasper Korsholm, MD
• Phone: 004578452254
• Email: kasperkorsholm[@]clin.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Atrial fibrillation (AF) is progressively common, and increases the risk of stroke five-fold. Oral anticoagulation is the mainstay therapy; however, it increases the risk of bleeding. Moreover, 30% with AF and at risk of stroke are not in relevant anticoagulation. The randomized PROTECT-AF trial has demonstrated the superiority of left atrial appendage occlusion (LAAO) as compared to warfarin for prevention of the combined endpoint of stroke, major bleeding and cardiovascular mortality. However, studies comparing LAAO to therapy with novel oral anticoagulants (NOAC) have not been carried out.

This study aims to assess the effect of left atrial appendage occlusion (LAAO) to reduce the incidence of stroke, systemic embolism, major bleeding and all-cause mortality in patients with atrial fibrillation (AF) and a prior ischemic stroke or transient ischemic attack (TIA).

Description:

An investigator-initiated multicenter, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). The active comparison LAAO is tested against NOAC therapy in a 1:1 stratified randomization. Patients should have AF, and an ischemic stroke or TIA within 6 months prior to enrollment. In total 750 patients will be included. Follow-up will be based on in-office and telephone follow-up during the first 3 years after randomization, along with up to 10 years long-term follow-up through the National Patient Registries.

The main study outcomes: The primary outcome is a composite of stroke (hemorrhagic or ischemic), systemic embolism, major bleeding or all-cause mortality assessed after at least two years follow-up for the last enrolled patient. Secondary outcomes will examine early and late safety outcome measures. The long-term outcome will be assessed up to 10-years after randomization through the National Patient Registries.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: October 1, 2030
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• documented non-valvular atrial fibrillation (paroxysmal, persistent or permanent)

• Eligible for long-term Novel Oral Anticoagulation (NOAC) therapy

• Ischemic stroke within the recent 6 months verified by neuroimaging, or

• Transient ischemic attack within 6 months with proven cerebral ischemia based on cerebral magnetic resonance imaging (MRI)

Exclusion Criteria:

• Modified rankin scale > 3 at time of enrollment

• Glomerular filtration rate (GFR) below 15 ml/min/1.73 m2

• Contraindication towards long-term aspirin therapy

• Planned combined cardiovascular interventional procedures at the time of enrollment

• Terminal illness or cancer with life expectancy less than 2 years.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Stroke

Intervention

Device:
• Left atrial appendage occlusion
Interventional left atrial appendage occlusion with the Amulet or Watchman device

Drug:
• NOAC
Medical treatment arm. Patients will be treated with one of the available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban. The specific drug and dose is at the discretion of the treating physician.

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg	The North Denmark Region
Denmark	Aarhus University Hospital	Aarhus	Central Denmark Region
Denmark	Rigshospitalet	Copenhagen
Denmark	Regional Hospital West Jutland	Holstebro
Denmark	Odense University Hospital	Odense	Region Of Southern Denmark
Finland	Helsinki University Central Hospital	Helsinki
Finland	Oulu University Hospital	Oulu
Finland	Turku University Hospital	Turku
Germany	Jena University Hospital	Jena
Norway	Haukeland University Hospital	Bergen
Norway	Oslo University Hospital	Oslo
Norway	Trondheim University Hospital	Trondheim
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Skånes University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm

Sponsors (14)

Lead Sponsor	Collaborator
University of Aarhus	Aalborg University Hospital, Aarhus University Hospital, Gødstrup Hospital, Haukeland University Hospital, Helsinki University Central Hospital, Jena University Hospital, Karolinska University Hospital, Lund University Hospital, Odense University Hospital, Oslo University Hospital, Rigshospitalet, Denmark, Sahlgrenska University Hospital, Sweden, Trondheim University Hospital

Countries where clinical trial is conducted

Denmark,  Finland,  Germany,  Norway,  Sweden, 

References & Publications (22)

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Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014 Jul 8;64(1):1-12. doi: 10.1016/j.jacc.2014.04.029. Erratum In: J Am Coll Cardiol. 2014 Sep 16;64(11):1186. — View Citation

Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210. Epub 2016 Aug 27. No abstract available. — View Citation

Landmesser U, Schmidt B, Nielsen-Kudsk JE, Lam SCC, Park JW, Tarantini G, Cruz-Gonzalez I, Geist V, Della Bella P, Colombo A, Zeus T, Omran H, Piorkowski C, Lund J, Tondo C, Hildick-Smith D. Left atrial appendage occlusion with the AMPLATZER Amulet device: periprocedural and early clinical/echocardiographic data from a global prospective observational study. EuroIntervention. 2017 Sep 20;13(7):867-876. doi: 10.4244/EIJ-D-17-00493. — View Citation

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Sahay S, Nombela-Franco L, Rodes-Cabau J, Jimenez-Quevedo P, Salinas P, Biagioni C, Nunez-Gil I, Gonzalo N, de Agustin JA, Del Trigo M, Perez de Isla L, Fernandez-Ortiz A, Escaned J, Macaya C. Efficacy and safety of left atrial appendage closure versus medical treatment in atrial fibrillation: a network meta-analysis from randomised trials. Heart. 2017 Jan 15;103(2):139-147. doi: 10.1136/heartjnl-2016-309782. Epub 2016 Sep 1. — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minor bleeding	Any bleeding clinically mentionable that does not qualify as life-threatening, disabling or major.	24 months
Other	Comparison of the cost-effectiveness of LAAO and NOAC therapy	All costs and cost-effectiveness will be evaluated and compared between the two diagnostic strategies.	24 months
Primary	Composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, major bleeding and all-cause mortality.	The primary endpoint is the combined rate of stroke, systemic embolism, major bleeding and all-cause mortality.	Up to 5-years from randomization
Secondary	Incidence of ischemic stroke	The occurrence of an acute onset of a focal neurological deficit of presumed vascular origin lasting for = 24 hours or resulting in death. Stroke is categorized as ischemic based on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain or autopsy.	2-, 3-, 5- and 10-years
Secondary	Incidence of hemorrhagic stroke	The occurrence of an acute onset of a focal neurological deficit of presumed vascular origin lasting for = 24 hours or resulting in death. Stroke is categorized as hemorrhagic based on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain or autopsy.	2-, 3-, 5- and 10-years
Secondary	Incidence of systemic embolism	The occurrence of an acute vascular insufficiency or occlusion of the extremities or any non-CNS organ associated with clinical, imaging, surgical or autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g. trauma, atherosclerosis, or instrumentation).	2-, 3-, 5- and 10-years
Secondary	Incidence of major or life-threatening bleeding	The occurrence of an overt bleeding associated with one or more of the following: decrease in hemoglobin of at least 3.0 g/dL, transfusion of 2 or more units of blood, causing hospitalization, requiring surgery, causing discontinuation of all antithrombotic therapy or pericardial bleeding with/without tamponade or occurring during the index LAAO procedure or during hospitalization for the index procedure (major bleeding). Life-threatening bleeding is defined as fatal bleeding, causing hypovolaemic shock or severe hypotension requiring vasopressor therapy or intervention, symptomatic bleeding in a critical organ (intracranial, intraspinal, intraocular, intramuscular with compartment syndrome, pericardial bleeding after hospitalization for the index LAAO) or overt bleeding with decrease in hemoglobin = 5 g/dL or requiring transfusion of = 4 units of blood.	2-, 3-, 5- and 10-years
Secondary	Incidence of all-cause mortality	The occurrence of death from any cause	2-, 3-, 5- and 10-years
Secondary	Incidence of Transient ischemic attack (TIA)	an episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischemia leading to symptoms lasting less than 24 hours, without acute infarction based on neuroimaging.	2-, 3-, 5- and 10-years
Secondary	Number of patients with a device-related complication	A complication related to the presence of the device. Device-related complications include: Device embolization; Device erosion; Clinically significant device interference with surrounding structures. This includes structures at the implant location (circumflex coronary artery, mitral valve, pulmonary artery, pulmonary vein) or cardiovascular structures in the vicinity of the location to which the device migrated (if applicable).; Device thrombus; Device fracture; Device infection/endocarditis/pericarditis; Device perforation/laceration; Device allergy	2 months
Secondary	Number of patients with a procedure-related complication	All complications related to the LAAO-procedure will be assessed.	2 months
Secondary	Number of patients with a device success	Device deployed and implanted in correct position	2 months
Secondary	Number of patients with technical success	Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak >5 mm on color Doppler TEE.	2 Months
Secondary	Number of patients with procedural success	Technical success and no procedure-related complications, except uncomplicated device embolization (i.e. device embolization resolved by percutaneous retrieval during the procedure without surgical intervention or damage to surrounding cardiovascular structures).	2 months
Secondary	Number of patients with peri-device leaks at follow-up imaging	Detection of any peri-device flow/gap at follow-up cardiac CT/TEE.	2 months
Secondary	Changes in functional status based on Modified Rankin Scale	The Modified Rankin scale is used to measure the degree of disability or dependence in daily activities caused by a stroke. The scale runs from 0-6, from no symptoms (0) to death (6).	24 months
Secondary	Changes in Quality of life	Based on patient self-reported EuroQol-5D questionnaires. The EuroQol-5D is a standardized instrument to measure health-related quality of life. It includes five self-rated dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The questionnaire have 3 levels of severity for each of the five dimensions. It also includes a visual scale from 0 (worst thinkable health condition) to 100 (best thinkable health condition) to report an overall measure.	12 months
Secondary	Compliance to NOAC	Adherence to assigned NOAC therapy will be assessed through the National Prescription Registries.	2-, 3-, 5-, and 10-years
Secondary	Changes in neurological status based on National Institute of Health (NIH) Stroke scale score	Assessed by the NIH stroke scale at baseline and 12 month follow-up. A scale to quantify the neurological impairment caused by a stroke. It includes 11 items, each of which scores a specific ability between 0 to 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores are summed to calculate the total NIH Stroke Scale score, that can range from 0 to 42, with 0 being no symptoms.; Score 0: No stroke symptoms; Score 1-4: Minor stroke; Score 5-15: Moderate stroke; Score 16-20: Moderate to severe stroke; Score 21-42: Severe stroke	12 months