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

Not Applicable

Completed

• Conditions: Ischemic Stroke; Atrial Fibrillation
• Interventions: Other: Late start of NOAC; Other: Early start of NOAC

• Registration Number: NCT02961348
• Lead Sponsor: Uppsala University

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.

Study Timeline

• Study First Submitted: 2016-11-08
• Study First Submitted QC: 2016-11-08
• Study First Posted: 2016-11-10
• Study Start: 2017-02-15
• Primary Completion: 2021-06-10
• Study Completion: 2024-04-30
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-15
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 888

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Late start of NOAC	Late start of NOAC	Day 5 to day 10 after ischemic stroke onset
Early start of NOAC	Early start of NOAC	Day 1 to day 4 after ischemic stroke onset

Primary Outcome Measures

Name	Time	Method
Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality	90 days

Secondary Outcome Measures

Name	Time	Method
Recurrent acute ischemic stroke	90 days	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)	90 days	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	90 days
Functional outcome	90 days	Defined by grade on the modified Rankin Scale (mRS)
Major hemorrhages	90 days	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

Trial Locations

Locations (35)

Alingås Hospital; 🇸🇪 Alingsås, Sweden

Enköping Hospital; 🇸🇪 Enköping, Sweden

Mälarsjukhuset Hospital; 🇸🇪 Eskilstuna, Sweden

Sahlgrenska University Hospital; 🇸🇪 Göteborg, Sweden

Falu Hospital; 🇸🇪 Falun, Sweden

Gävle Hospital; 🇸🇪 Gävle, Sweden

Sahlgrenska University Hospital Östra; 🇸🇪 Göteborg, Sweden

Hallands Hospital; 🇸🇪 Varberg, Sweden

Helsingborg Hospital; 🇸🇪 Helsingborg, Sweden

Karolinska University Hospital - Huddinge; 🇸🇪 Huddinge, Sweden

Hudiksvalls sjukhus; 🇸🇪 Hudiksvall, Sweden

Hässleholm Hospital; 🇸🇪 Hässleholm, Sweden

Ryhov; 🇸🇪 Jönköping, Sweden

Kalmar Hopsital; 🇸🇪 Kalmar, Sweden

Köping Hospital; 🇸🇪 Köping, Sweden

Länssjukhuset Kalmar; 🇸🇪 Kalmar, Sweden

Kiruna Hospital; 🇸🇪 Kiruna, Sweden

Kungälv Hospital; 🇸🇪 Kungälv, Sweden

Lund; 🇸🇪 Lund, Sweden

Motala Hospital; 🇸🇪 Motala, Sweden

Lindesberg Hospital; 🇸🇪 Lindesberg, Sweden

Malmö University Hospital; 🇸🇪 Malmö, Sweden

Sahlgrenska Universitetssjukhuset Mölndal; 🇸🇪 Mölndal, Sweden

Nyköping Hospital; 🇸🇪 Nyköping, Sweden

Oskarshamn Hospital; 🇸🇪 Oskarshamn, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Skaraborg Hospital; 🇸🇪 Skövde, Sweden

Danderyd University Hospital; 🇸🇪 Stockholm, Sweden

Capio S:t Görans Hospital; 🇸🇪 Stockholm, Sweden

Södersjukhuset; 🇸🇪 Stockholm, Sweden

University Hospital of Umeå; 🇸🇪 Umeå, Sweden

Sundsvall County Hospital; 🇸🇪 Sundsvall, Sweden

Västerås Hospital; 🇸🇪 Västerås, Sweden

Örebro University Hospital; 🇸🇪 Örebro, Sweden

Karolinska University Hospital; 🇸🇪 Solna, Sweden