TIMING of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02961348
• Other study ID #: U-2015-341
• Secondary ID: 2015-00881
• Status: Completed
• Phase: N/A
• Start date: February 15, 2017
• Est. completion date: April 30, 2024

Study information

• Verified date: May 2024
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 888
• Est. completion date: April 30, 2024
• Est. primary completion date: June 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Other:
• Early start of NOAC
Initiation of NOAC up until day 4 after acute ischemic stroke in patients with atrial fibrillation
• Late start of NOAC
Initiation of NOAC between day 5 and day 10 after acute ischemic stroke in patients with atrial fibrillation

Locations

Country	Name	City	State
Sweden	Alingås Hospital	Alingsås
Sweden	Enköping Hospital	Enköping
Sweden	Mälarsjukhuset Hospital	Eskilstuna
Sweden	Falu Hospital	Falun
Sweden	Gävle Hospital	Gävle
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Sahlgrenska University Hospital Östra	Göteborg
Sweden	Hallands Hospital	Halmstad
Sweden	Hässleholm Hospital	Hässleholm
Sweden	Helsingborg Hospital	Helsingborg
Sweden	Karolinska University Hospital - Huddinge	Huddinge
Sweden	Hudiksvalls sjukhus	Hudiksvall
Sweden	Ryhov	Jönköping
Sweden	Kalmar Hopsital	Kalmar
Sweden	Länssjukhuset Kalmar	Kalmar
Sweden	Kiruna Hospital	Kiruna
Sweden	Köping Hospital	Köping
Sweden	Kungälv Hospital	Kungälv
Sweden	Lindesberg Hospital	Lindesberg
Sweden	Lund	Lund
Sweden	Malmö University Hospital	Malmö
Sweden	Sahlgrenska Universitetssjukhuset Mölndal	Mölndal
Sweden	Motala Hospital	Motala
Sweden	Nyköping Hospital	Nyköping
Sweden	Örebro University Hospital	Örebro
Sweden	Oskarshamn Hospital	Oskarshamn
Sweden	Skaraborg Hospital	Skövde
Sweden	Karolinska University Hospital	Solna
Sweden	Capio S:t Görans Hospital	Stockholm
Sweden	Danderyd University Hospital	Stockholm
Sweden	Södersjukhuset	Stockholm
Sweden	Sundsvall County Hospital	Sundsvall
Sweden	University Hospital of Umeå	Umeå
Sweden	Uppsala University Hospital	Uppsala
Sweden	Hallands Hospital	Varberg
Sweden	Västerås Hospital	Västerås

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	The Swedish Stroke Register (Riksstroke)

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

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. — View 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 Random — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality		90 days
Secondary	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	90 days
Secondary	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	90 days
Secondary	All-cause mortality		90 days
Secondary	Functional outcome	Defined by grade on the modified Rankin Scale (mRS)	90 days
Secondary	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	90 days