TIMING of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation
Primary Purpose
Ischemic Stroke, Atrial Fibrillation
Status
Active
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Early start of NOAC
Late start of NOAC
Sponsored by
About this trial
This is an interventional prevention trial for Ischemic Stroke focused on measuring Oral anticoagulants (NOAC)
Eligibility Criteria
Inclusion Criteria:
- Adult patients (≥ 18 years) with acute ischemic stroke and atrial fibrillation
- Eligible and willing to start (or re-start) NOAC
- Registered in The Swedish Stroke Register
- Signed informed consent
Exclusion Criteria:
- Contraindication to NOAC (e.g. ongoing bleeding, mechanical heart valve prosthesis)
- Ongoing therapy with NOAC (without ≥2 days interruption at index stroke)
- International normalized ratio (INR)>1.7
- No second brain imaging (CT/MRI) after thrombolysis/thrombectomy
- Previous randomization in the TIMING study
Sites / Locations
- Alingås Hospital
- Enköping Hospital
- Mälarsjukhuset Hospital
- Falu Hospital
- Gävle Hospital
- Sahlgrenska University Hospital Östra
- Sahlgrenska University Hospital
- Hallands Hospital
- Helsingborg Hospital
- Karolinska University Hospital - Huddinge
- Hudiksvalls sjukhus
- Hässleholm Hospital
- Ryhov
- Kalmar Hopsital
- Länssjukhuset Kalmar
- Kiruna Hospital
- Kungälv Hospital
- Köping Hospital
- Lindesberg Hospital
- Lund
- Malmö University Hospital
- Motala Hospital
- Sahlgrenska Universitetssjukhuset Mölndal
- Nyköping Hospital
- Oskarshamn Hospital
- Skaraborg Hospital
- Karolinska University Hospital
- Capio S:t Görans Hospital
- Danderyd University Hospital
- Södersjukhuset
- Sundsvall County Hospital
- University Hospital of Umeå
- Uppsala University Hospital
- Hallands Hospital
- Västerås Hospital
- Örebro University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Early start of NOAC
Late start of NOAC
Arm Description
Day 1 to day 4 after ischemic stroke onset
Day 5 to day 10 after ischemic stroke onset
Outcomes
Primary Outcome Measures
Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality
Secondary Outcome Measures
Recurrent acute ischemic stroke
Defined as a new focal neurological deficit of sudden onset lasting at least 24 h (or <24 h if following therapeutic intervention, i.e. thrombolysis or thrombectomy, or if the deficit results in death < 24 h), occurring >24 hours after the index ischemic stroke, irrespective of vascular territory and that is not attributable to edema, brain shift, hemorrhagic transformation, intercurrent illness, hypoxia, or drug toxicity
Symptomatic intracerebral hemorrhage (S-ICH)
Defined as a new focal neurological deficit of sudden onset lasting at least 24 h with documented intracerebral hemorrhage (ICH) on imaging (computed tomography (CT) or magnetic resonance imaging (MRI)). Any intraparenchymal hematoma (≥10mm) will be considered, including hemorrhagic transformation of the index ischemic stroke. However microhemorrhages (<10mm) are not considered to be an ICH. ICH will be classified as symptomatic if it is associated with ≥4 points in total NIHSS or ≥2 points in one NIHSS category
All-cause mortality
Functional outcome
Defined by grade on the modified Rankin Scale (mRS)
Major hemorrhages
Defined as bleedings that are fatal or life-threatening (according to the definition by the International Society on Thrombosis and Haemostasis) or lead to hospitalization
Full Information
NCT ID
NCT02961348
First Posted
November 8, 2016
Last Updated
May 17, 2022
Sponsor
Uppsala University
Collaborators
The Swedish Stroke Register (Riksstroke)
1. Study Identification
Unique Protocol Identification Number
NCT02961348
Brief Title
TIMING of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation
Official Title
Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation: a Prospective Multicenter Registry-based Non-inferiority Randomized Controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 15, 2017 (Actual)
Primary Completion Date
June 10, 2021 (Actual)
Study Completion Date
June 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
Collaborators
The Swedish Stroke Register (Riksstroke)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will compare early with late start of treatment with Non-vitamin K oral anticoagulation (NOAC) in adult patients with acute ischemic stroke and atrial fibrillation; it is a registry-based randomized clinical trial (R-RCT) using The Swedish Stroke Register (Riksstroke). Half of the patients will start NOAC early (within 4 days after stroke onset) while the other half will start late (5-10 days after stroke onset).
Detailed Description
Oral anticoagulation therapy is well established and highly recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation, but the optimal time point to start after an acute ischemic stroke is not known.
The intervention in this study will be timing of treatment onset. The choice of NOAC (i.e. apixaban, dabigatran, edoxaban or rivaroxaban) after the acute ischemic stroke is at the discretion of the treating physician.
This study will use the Swedish Stroke Register for enrolment, randomization and follow-up, with additional data linkage from other mandatory national registers. Primary outcome will be assessed at 90 days and secondary outcomes (including all-cause mortality and health economic analyses) and will be assessed at 90 days and up to one year after the index ischemic stroke.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Atrial Fibrillation
Keywords
Oral anticoagulants (NOAC)
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
888 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Early start of NOAC
Arm Type
Active Comparator
Arm Description
Day 1 to day 4 after ischemic stroke onset
Arm Title
Late start of NOAC
Arm Type
Active Comparator
Arm Description
Day 5 to day 10 after ischemic stroke onset
Intervention Type
Other
Intervention Name(s)
Early start of NOAC
Intervention Description
Initiation of NOAC up until day 4 after acute ischemic stroke in patients with atrial fibrillation
Intervention Type
Other
Intervention Name(s)
Late start of NOAC
Intervention Description
Initiation of NOAC between day 5 and day 10 after acute ischemic stroke in patients with atrial fibrillation
Primary Outcome Measure Information:
Title
Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Recurrent acute ischemic stroke
Description
Defined as a new focal neurological deficit of sudden onset lasting at least 24 h (or <24 h if following therapeutic intervention, i.e. thrombolysis or thrombectomy, or if the deficit results in death < 24 h), occurring >24 hours after the index ischemic stroke, irrespective of vascular territory and that is not attributable to edema, brain shift, hemorrhagic transformation, intercurrent illness, hypoxia, or drug toxicity
Time Frame
90 days
Title
Symptomatic intracerebral hemorrhage (S-ICH)
Description
Defined as a new focal neurological deficit of sudden onset lasting at least 24 h with documented intracerebral hemorrhage (ICH) on imaging (computed tomography (CT) or magnetic resonance imaging (MRI)). Any intraparenchymal hematoma (≥10mm) will be considered, including hemorrhagic transformation of the index ischemic stroke. However microhemorrhages (<10mm) are not considered to be an ICH. ICH will be classified as symptomatic if it is associated with ≥4 points in total NIHSS or ≥2 points in one NIHSS category
Time Frame
90 days
Title
All-cause mortality
Time Frame
90 days
Title
Functional outcome
Description
Defined by grade on the modified Rankin Scale (mRS)
Time Frame
90 days
Title
Major hemorrhages
Description
Defined as bleedings that are fatal or life-threatening (according to the definition by the International Society on Thrombosis and Haemostasis) or lead to hospitalization
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients (≥ 18 years) with acute ischemic stroke and atrial fibrillation
Eligible and willing to start (or re-start) NOAC
Registered in The Swedish Stroke Register
Signed informed consent
Exclusion Criteria:
Contraindication to NOAC (e.g. ongoing bleeding, mechanical heart valve prosthesis)
Ongoing therapy with NOAC (without ≥2 days interruption at index stroke)
International normalized ratio (INR)>1.7
No second brain imaging (CT/MRI) after thrombolysis/thrombectomy
Previous randomization in the TIMING study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonas Oldgren, MD. PhD
Organizational Affiliation
Dept of Medical Sciences, Uppsala University, Sweden
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Signild Åsberg, MD. PhD
Organizational Affiliation
Dept of Medical Sciences, Uppsala University, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alingås Hospital
City
Alingsås
Country
Sweden
Facility Name
Enköping Hospital
City
Enköping
Country
Sweden
Facility Name
Mälarsjukhuset Hospital
City
Eskilstuna
Country
Sweden
Facility Name
Falu Hospital
City
Falun
Country
Sweden
Facility Name
Gävle Hospital
City
Gävle
Country
Sweden
Facility Name
Sahlgrenska University Hospital Östra
City
Göteborg
Country
Sweden
Facility Name
Sahlgrenska University Hospital
City
Göteborg
Country
Sweden
Facility Name
Hallands Hospital
City
Halmstad
Country
Sweden
Facility Name
Helsingborg Hospital
City
Helsingborg
Country
Sweden
Facility Name
Karolinska University Hospital - Huddinge
City
Huddinge
Country
Sweden
Facility Name
Hudiksvalls sjukhus
City
Hudiksvall
Country
Sweden
Facility Name
Hässleholm Hospital
City
Hässleholm
Country
Sweden
Facility Name
Ryhov
City
Jönköping
Country
Sweden
Facility Name
Kalmar Hopsital
City
Kalmar
Country
Sweden
Facility Name
Länssjukhuset Kalmar
City
Kalmar
Country
Sweden
Facility Name
Kiruna Hospital
City
Kiruna
Country
Sweden
Facility Name
Kungälv Hospital
City
Kungälv
Country
Sweden
Facility Name
Köping Hospital
City
Köping
Country
Sweden
Facility Name
Lindesberg Hospital
City
Lindesberg
Country
Sweden
Facility Name
Lund
City
Lund
Country
Sweden
Facility Name
Malmö University Hospital
City
Malmö
Country
Sweden
Facility Name
Motala Hospital
City
Motala
Country
Sweden
Facility Name
Sahlgrenska Universitetssjukhuset Mölndal
City
Mölndal
Country
Sweden
Facility Name
Nyköping Hospital
City
Nyköping
Country
Sweden
Facility Name
Oskarshamn Hospital
City
Oskarshamn
Country
Sweden
Facility Name
Skaraborg Hospital
City
Skövde
Country
Sweden
Facility Name
Karolinska University Hospital
City
Solna
Country
Sweden
Facility Name
Capio S:t Görans Hospital
City
Stockholm
Country
Sweden
Facility Name
Danderyd University Hospital
City
Stockholm
Country
Sweden
Facility Name
Södersjukhuset
City
Stockholm
Country
Sweden
Facility Name
Sundsvall County Hospital
City
Sundsvall
Country
Sweden
Facility Name
University Hospital of Umeå
City
Umeå
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden
Facility Name
Hallands Hospital
City
Varberg
Country
Sweden
Facility Name
Västerås Hospital
City
Västerås
Country
Sweden
Facility Name
Örebro University Hospital
City
Örebro
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36065821
Citation
Oldgren J, Asberg S, Hijazi Z, Wester P, Bertilsson M, Norrving B; National TIMING Collaborators. Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study. Circulation. 2022 Oct 4;146(14):1056-1066. doi: 10.1161/CIRCULATIONAHA.122.060666. Epub 2022 Sep 6. Erratum In: Circulation. 2022 Nov 8;146(19):e279.
Results Reference
derived
PubMed Identifier
29197413
Citation
Asberg S, Hijazi Z, Norrving B, Terent A, Ohagen P, Oldgren J. Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial. Trials. 2017 Dec 2;18(1):581. doi: 10.1186/s13063-017-2313-9.
Results Reference
derived
Learn more about this trial
TIMING of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation
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