Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage
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|ClinicalTrials.gov Identifier: NCT02830152|
Recruitment Status : Recruiting
First Posted : July 12, 2016
Last Update Posted : May 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation Stroke Intracerebral Hemorrhage||Device: LAAO Drug: Medical Therapy||Not Applicable|
Methods/design: A multicenter prospective randomized open-label clinical trial with blinded outcome evaluation (PROBE design) and blinded safety outcome assessment. The active comparison LAAO is tested against medical therapy in a 2:1 stratified randomization.
Study population: Patients should have had an ICH within 6 months prior to enrollment and have NVAF with increased risk of stroke or systemic embolism, as indicated by a CHA2DS2VASc score >2. In total 750 patients will be included. Active enrollment ensues over 3 years followed by 5 years follow-up and a long-term follow-up at 10 years.
Intervention and control: The intervention group will be treated by LAAO, using the Amplatzer Amulet device. Implantation requires a catheterization procedure using venous access and transseptal puncture and is guided by angiography, fluoroscopy and transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE). Recommended post-implant antithrombotic therapy includes aspirin (ASA) therapy for at least 6 months, with or without clopidogrel for the first 45 days after implantation. The control group will receive medical therapy, delivered according to national standards and guidelines at the treating physicians' discretion. This may include oral anticoagulation (OAC) (vitamin-K antagonists, VKA), non-VKA OAC, antiplatelet therapy or no antithrombotic therapy at all.
Main study outcomes: The primary outcome is the composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality, assessed over at least two years. Secondary outcome examines various early and late safety outcome parameters.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||750 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage: A Multicenter Randomized Clinical Trial|
|Actual Study Start Date :||May 3, 2017|
|Estimated Primary Completion Date :||May 2022|
|Estimated Study Completion Date :||May 2030|
Experimental: Left Atrial Appendage Occlusion (LAAO)
The intervention is implantation of Amplatzer Amulet LAAO device within two months after randomization. Device implantation comprises a catheterization procedure using venous access and a transseptal puncture to obtain access to the left atrium (LA). Procedural imaging guidance is left to the physician's discretion and may include several techniques such as angiography/fluoroscopy, transesophageal echocardiography (TEE) and/or intracardiac echocardiography (ICE). Recommended post-implant antithrombotic therapy includes ASA therapy for at least 6 months, which may be combined with clopidogrel for the first 45 days after implantation.
The left atrial appendage is occluded with the AMPLATZER™ Amulet™ device, which offers a conformable disc and lobe designed for complete occlusion of the left atrial appendage.
Other Name: AMPLATZER™ Amulet™ (St. Jude Medical)
Active Comparator: Medical Therapy
The optimal medical therapy of stroke prevention in non-valvular atrial fibrillation (NVAF) after intracerebral hemorrhage (ICH) is not known. Therefore, it will be left to the discretion of the treating physician to decide if, when, and which pharmacological therapy will be prescribed. Available options include anticoagulation with oral anticoagulation (OAC) or novel oral anticoagulants (NOAC), antiplatelet therapy (including monotherapy and dual antiplatelet therapy) and no pharmacological antithrombotic therapy.
Drug: Medical Therapy
Available options included in Medical therapy are: anticoagulation with OAC or NOAC, antiplatelet therapy (including monotherapy and dual antiplatelet therapy) and no pharmacological antithrombotic therapy.
- Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality [ Time Frame: up to 5 years after randomization ]
This endpoint will be assessed in patients with paroxysmal, persistent or long-standing NVAF and with ICH within 6 months prior to enrollment.
The effect of LAAO will be compared to medical therapy at the treating physician's discretion as a control.
- Number of participants with a device-related complication [ Time Frame: up to 45 days after randomization ]
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
- Number of Participants with a device success [ Time Frame: up to 45 days after randomization ]Device deployed and implanted in correct position.
- Number of Participants with a Technical success [ Time Frame: up to 45 days after randomization ]Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak >5 mm on color Doppler TEE.
- Number of Participants with a Procedural success [ Time Frame: up to 45 days after randomization ]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).
- Number of Participants with Significant peridevice leak [ Time Frame: up to 45 days after randomization ]Consistent with the definition of technical success, a significant peridevice leak is defined as a leak shown as a jet >5 mm on color Doppler TEE.
- Compare the functional status prior to and post treatment [ Time Frame: 24 months after randomization ]The Modified Rankin Scale (mRS) will be used for measuring the Functional status.
- Compare the cognitive status prior to and post treatment [ Time Frame: 24 months after randomization ]The cognitive status will be assessed by using Montreal Cognitive Assessment (MOCA) and Mini-mental state examination (MMSE)
- Compare the neurological status prior to and post treatment [ Time Frame: 24 months after randomization ]The National Institutes of Health Stroke Scale (NIHSS) is used to assess the neurological status
- Compare the quality of life prior to and post treatment by using EuroQol [ Time Frame: 24 months after randomization ]
- Late safety outcome parameters of LAAO and Medical therapy [ Time Frame: up to 10 years after randomization ]Stroke (ischemic or hemorrhagic), systemic embolism, bleeding, all-cause mortality, intracranial hemorrhage, cardiovascular mortality and unplanned hospitalization will be evaluated
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02830152
|Contact: Berit Larsson||+46 72 580 29 email@example.com|
|Sahlrenska University Hospital||Recruiting|
|Contact: Jacob Odenstedt firstname.lastname@example.org|
|Danderyd Hospital||Active, not recruiting|
|Principal Investigator:||Mårten Rosenqvist, MD||Karolinska Institutet|