Clinical trial NCT02961348: 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
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Atrial Fibrillation
Keywords: Oral anticoagulants (NOAC)
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: The Swedish Stroke Register (Riksstroke)
First posted: 2016-11-10
Enrollment: 888
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality
timeFrame: 90 days
Secondary outcomes:
measure: Recurrent acute ischemic stroke
timeFrame: 90 days
measure: Symptomatic intracerebral hemorrhage (S-ICH)
timeFrame: 90 days
measure: All-cause mortality
timeFrame: 90 days
measure: Functional outcome
timeFrame: 90 days
measure: Major hemorrhages
timeFrame: 90 days
Other outcomes:
Locations:
city: Alingsås
country: Sweden
facility: Alingås Hospital
city: Enköping
country: Sweden
facility: Enköping Hospital
city: Eskilstuna
country: Sweden
facility: Mälarsjukhuset Hospital
city: Falun
country: Sweden
facility: Falu Hospital
city: Gävle
country: Sweden
facility: Gävle Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital Östra
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Halmstad
country: Sweden
facility: Hallands Hospital
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Huddinge
country: Sweden
facility: Karolinska University Hospital - Huddinge
city: Hudiksvall
country: Sweden
facility: Hudiksvalls sjukhus
city: Hässleholm
country: Sweden
facility: Hässleholm Hospital
city: Jönköping
country: Sweden
facility: Ryhov
city: Kalmar
country: Sweden
facility: Kalmar Hopsital
city: Kalmar
country: Sweden
facility: Länssjukhuset Kalmar
city: Kiruna
country: Sweden
facility: Kiruna Hospital
city: Kungälv
country: Sweden
facility: Kungälv Hospital
city: Köping
country: Sweden
facility: Köping Hospital
city: Lindesberg
country: Sweden
facility: Lindesberg Hospital
city: Lund
country: Sweden
facility: Lund
city: Malmö
country: Sweden
facility: Malmö University Hospital
city: Motala
country: Sweden
facility: Motala Hospital
city: Mölndal
country: Sweden
facility: Sahlgrenska Universitetssjukhuset Mölndal
city: Nyköping
country: Sweden
facility: Nyköping Hospital
city: Oskarshamn
country: Sweden
facility: Oskarshamn Hospital
city: Skövde
country: Sweden
facility: Skaraborg Hospital
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Capio S:t Görans Hospital
city: Stockholm
country: Sweden
facility: Danderyd University Hospital
city: Stockholm
country: Sweden
facility: Södersjukhuset
city: Sundsvall
country: Sweden
facility: Sundsvall County Hospital
city: Umeå
country: Sweden
facility: University Hospital of Umeå
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Varberg
country: Sweden
facility: Hallands Hospital
city: Västerås
country: Sweden
facility: Västerås Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Dept of Medical Sciences, Uppsala University, Sweden
name: Jonas Oldgren, MD. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept of Medical Sciences, Uppsala University, Sweden
name: Signild Åsberg, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.