Atrial FibrillationNCT02830152
Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage
A study testing LAAO and Medical Therapy in people with Atrial Fibrillation and Stroke, run by Karolinska Institutet at 17 sites in 4 countries.
Trial summary
Intracerebral hemorrhage (ICH) in patients with non-valvular atrial fibrillation (NVAF) poses a particular dilemma for thromboprophylaxis. Left atrial appendage occlusion (LAAO) is a non-pharmacological approach to prevent cardiac embolism in NVAF. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Stroke, Intracerebral Hemorrhage
- What is being tested?
- LAAO and Medical Therapy
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 750 participants
- Where
- 17 sitesin 4 countries
- Study dates
- 3 May 2017to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A diagnosis of paroxysmal, persistent or long-standing NVAF with CHA2DS2VASc score >2.
- Clinical and CT/MRI evidence of ICH within 12 months but not less than 4 weeks prior to enrollment.
- Age > 18 years.
- Signed informed consent.
Who cannot join
- ICH secondary to vascular malformation or tumors
- Estimated life expectancy of less than 1 year at eligibility assessment
- mRS > 3 at enrollment
- Prior surgical LAA excision
- Planned combined interventional procedures at the time of enrollment
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
Denmark5 sites
Aarhus University Hospital
Aarhus
Bispebjerg University Hospital
Bispebjerg
Rikshospitalet Glostrup
Glostrup Municipality
Herlev sjukhus
Herlev
Odenses Universitetssjukhus
Odense
Finland5 sites
Helsinki University Hospital
Helsinki
North Karelia Central Hospital
Joensuu
Kuopio University Hospital
Kuopio
Turku University Hospital
Turku
Vaasa Centralsjukhus
Vaasa
Sweden5 sites
Sahlgrenska University Hospital
Gothenburg
Universitetssjukhuset Skåne
Lund
Universitetssjukhuset
Örebro
Danderyd Hospital
Stockholm
Akademiska sjukhuset
Uppsala
Norway2 sites
Haukeland Universitetssjukhus
Bergen
Oslo University Hospital
Oslo
About this study
Official title: Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage: A Multicenter Randomized Clinical Trial
Intracerebral hemorrhage (ICH) in patients with non-valvular atrial fibrillation (NVAF) poses a particular dilemma for thromboprophylaxis. Left atrial appendage occlusion (LAAO) is a non-pharmacological approach to prevent cardiac embolism in NVAF. The risk-benefit ratio of LAAO in patients with NVAF after ICH is unknown. The aim of STROKECLOSE is to assess the effect of LAAO to reduce the incidence stroke, bleeding and cardiovascular mortality in patients with NVAF and prior ICH.
Read the detailed description
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 12 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.
- Conditions
- Atrial Fibrillation, Stroke, Intracerebral Hemorrhage
- Being tested
- LAAO, Medical Therapy
- Keywords
- Stroke, intracerebral hemorrhage, left atrial appendage occlusion, atrial fibrillation, oral anticoagulation, preventive therapy
- Medical subject headings
- Atrial Fibrillation, Stroke, Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAAODevice
Also called AMPLATZER™ Amulet™ (St. Jude Medical)
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.
Medical TherapyDrug
Also called Antiplatelet 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.
| Study group | Role | What they receive |
|---|---|---|
| Left Atrial Appendage Occlusion (LAAO) | Experimental | 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. Receives: Device: LAAO |
| Medical Therapy | Active comparator | 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. Receives: Drug: Medical Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality
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.
Measured: up to 5 years after randomization
Secondary outcomes (10)
Number of participants 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
Measured: up to 45 days after randomization
Number of Participants with a device success
Device deployed and implanted in correct position.
Measured: up to 45 days after randomization
Number of Participants with a Technical success
Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak >5 mm on color Doppler TEE.
Measured: up to 45 days after randomization
Number of Participants with a 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).
Measured: up to 45 days after randomization
Number of Participants with Significant peridevice leak
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.
Measured: up to 45 days after randomization
Compare the functional status prior to and post treatment
The Modified Rankin Scale (mRS) will be used for measuring the Functional status.
Measured: 24 months after randomization
Compare the cognitive status prior to and post treatment
The cognitive status will be assessed by using Montreal Cognitive Assessment (MOCA) and Mini-mental state examination (MMSE)
Measured: 24 months after randomization
Compare the neurological status prior to and post treatment
The National Institutes of Health Stroke Scale (NIHSS) is used to assess the neurological status
Measured: 24 months after randomization
Compare the quality of life prior to and post treatment by using EuroQol
EuroQol assesses health status in terms of five dimension: mobility (walking about); looking after myself; doing usual activities (e.g., going to school, hobbies, sports, playing, doing things with family and friends); having pain or discomfort; and feeling worried, sad, or unhappy. The levels for the dimensions are: 'none/no problems', 'some (problems)', and 'a lot (of problems)'. Higher score represents more problems.
Measured: 24 months after randomization
Late safety outcome parameters of LAAO and Medical therapy
Stroke (ischemic or hemorrhagic), systemic embolism, bleeding, all-cause mortality, intracranial hemorrhage, cardiovascular mortality and unplanned hospitalization will be evaluated
Measured: up to 10 years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2016 (estimated)
- Study start3 May 2017
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 750 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott Medical Devices
- Responsible party
- Principal investigator, Per Wester, Karolinska Institutet
- Investigators
- Per Wester, MD, Principal investigator, Department of Clinical Sciences, Karolinska Institute, Danderyds hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02830152
- Sponsor's protocol ID
- STROKECLOSE
- Status last verified
- Jun 2024
- First submitted
- 29 Jun 2016
- Last updated
- 12 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The full study protocol, statistical plan and informed consent form will be publicly available when results are published. Data will be available on patient level; data will be pseudonymized. The full dataset will be available upon request.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage: A Multicenter Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02830152
- Acronym / sponsor ID
- STROKECLOSE
- Conditions
- Atrial Fibrillation, Stroke, Intracerebral Hemorrhage
- Keywords
- Stroke, intracerebral hemorrhage, left atrial appendage occlusion, atrial fibrillation, oral anticoagulation, preventive therapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 750 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Abbott Medical Devices
- Study start
- 3 May 2017 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 12 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Intracerebral hemorrhage (ICH) in patients with non-valvular atrial fibrillation (NVAF) poses a particular dilemma for thromboprophylaxis. Left atrial appendage occlusion (LAAO) is a non-pharmacological approach to prevent cardiac embolism in NVAF. The risk-benefit ratio of LAAO in patients with NVAF after ICH is unknown. The aim of STROKECLOSE is to assess the effect of LAAO to reduce the incidence stroke, bleeding and cardiovascular mortality in patients with NVAF and prior ICH.
Detailed description
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 12 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Left Atrial Appendage Occlusion (LAAO) | Experimental | Device: LAAOThe 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. |
| Medical Therapy | Active comparator | Drug: Medical TherapyThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- A diagnosis of paroxysmal, persistent or long-standing NVAF with CHA2DS2VASc score >2.
- Clinical and CT/MRI evidence of ICH within 12 months but not less than 4 weeks prior to enrollment.
- Age > 18 years.
- Signed informed consent.
Key exclusion criteria (5 listed)
- ICH secondary to vascular malformation or tumors
- Estimated life expectancy of less than 1 year at eligibility assessment
- mRS > 3 at enrollment
- Prior surgical LAA excision
- Planned combined interventional procedures at the time of enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAAOAlso: AMPLATZER™ Amulet™ (St. Jude Medical)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. | Device | Left Atrial Appendage Occlusion (LAAO) |
| Medical TherapyAlso: Antiplatelet TherapyAvailable options included in Medical therapy are: anticoagulation with OAC or NOAC, antiplatelet therapy (including monotherapy and dual antiplatelet therapy) and no pharmacological antithrombotic therapy. | Drug | Medical Therapy |
Primary outcome
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.
10 secondary outcomes
Number of participants with a device-related complication
Time frame: up to 45 days after randomization
Number of Participants with a device success
Time frame: up to 45 days after randomization
Number of Participants with a Technical success
Time frame: up to 45 days after randomization
Number of Participants with a Procedural success
Time frame: up to 45 days after randomization
Number of Participants with Significant peridevice leak
Time frame: up to 45 days after randomization
Compare the functional status prior to and post treatment
Time frame: 24 months after randomization
Compare the cognitive status prior to and post treatment
Time frame: 24 months after randomization
Compare the neurological status prior to and post treatment
Time frame: 24 months after randomization
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Individual participant dataSharing planned: Yes. The full study protocol, statistical plan and informed consent form will be publicly available when results are published. Data will be available on patient level; data will be pseudonymized. The full dataset will be available upon request.
Related trials for Atrial Fibrillation
Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Wester, MD principal investigator
Department of Clinical Sciences, Karolinska Institute, Danderyds hospital
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LAAO and Medical Therapy in people with Atrial Fibrillation and Stroke, run by Karolinska Institutet at 17 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Denmark, Finland, Sweden, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.