Condition category
Circulatory System
Date applied
08/05/2018
Date assigned
15/05/2018
Last edited
14/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Patients who have had a stroke are at a higher risk of having further strokes if they suffer from an abnormal rhythm of the heart (atrial fibrillation). Research suggests that beginning therapy that reduces this risk of recurrent stroke should be done within 48 hours of the stroke. However, one of the risks of this therapy is that it causes an increased risk of bleeding in the area of the brain damaged by the stroke. If this occurs, the patient has a much higher risk of poor stroke outcome and death. The purpose of this research is to improve our understanding of the timing of initiation of blood-thinning therapy in stroke patients who have an abnormal rhythm of the heart (atrial fibrillation.
To do this we are observing patients in the hospital clinical setting who begin their anticoagulant (drug that prevents blood clotting) therapy within 7 days from their stroke or after 7 days from their stroke onset. We aim to measure evidence of new "recurrent" stroke as well as any bleeding events patients may have had at 90 days after the initial stroke. We aim to compare whether it is better for patients to receive this therapy within 7 days from their stroke or after 7 days.

Who can participate?
Adults who have had a stroke related to atrial fibrillation and have been treated with anticoagulants with 1 month of their stroke.

What does the study involve?
This is an observational study, which means that participants will receive usual treatment. Participants will have an additional MRI scan at 3 months after recruitment.

What are the possible benefits and risks of participating?
We cannot guarantee or promise that participants will receive any benefits from this project. MRI imaging is a very safe assessment for most patients, as it does not use radioactive substances. However, patients with heart pacemakers and other metallic surgical implants, for example a cochlear implant, cannot be scanned. Participants will be asked a safety questionnaire before their scan to ensure it is safe to be scanned. There are no other associated risks from participating in this study. Patients do not have to participate in this research project to receive any medical care that may be required. If patients choose not to participate they will receive the standard care that is given to patients experiencing stroke.

Where is the study run from?
Royal Melbourne Hospital

When is the study starting and how long is it expected to run for?
May 2016 to February 2019

Who is funding the study?
The Australasian Stroke Academy

Who is the main contact?
Ms Jillian Naylor, jnaylor@student.unimelb.edu.au



Trial website

Contact information

Type

Scientific

Primary contact

Prof Mark Parsons

ORCID ID

Contact details

Department of Neurology
Melbourne Brain Centre
Royal Melbourne Hospital
300 Grattan Street
Melbourne
3050
Australia

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2015-11-23 NOAC registry ATTUNE_v1.4.1final

Study information

Scientific title

A registry of clinical and MRI outcomes following early versus late initiation of anticoagulation after ischaemic stroke or transient ischaemic attack in patients with atrial fibrillation

Acronym

ATTUNE

Study hypothesis

1. Patients initiated on NOACs within 7 days of the stroke/TIA will have less recurrent infarction than patients initiated more than 7 days after their stroke/TIA
2. There will be no difference in haemorrhagic transformation (HT) or new intra-cerebral haemorrhage (ICH) in patients initiated on NOAC within 7 days of the stroke/TIA compared to initiation after 7 days
3. Patients initiated on NOAC within 7 days of the stroke/TIA will have fewer recurrent ischaemic events than patients initiated after 7 days
4. Early (<7 day) administration of oral anticoagulation will associate with a favorable overall cost-benefit ratio

Ethics approval

Hunter New England Human Research Ethics Committee, 12/04/2016, 16/02/17/4.01

Study design

Prospective observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Acute ischaemic stroke

Intervention

This is a prospective, 3-month observational cohort study using an established clinico-radiological stroke registry to examine clinical and MR imaging outcomes of patients initiated on novel oral anticoagulants (NOACs), including apixaban, rivaroxaban and dabigatran (note that edoxaban is currently unavailable in Australia) or vitamin K antagonists (VKAs), eg warfarin, within 1 month after acute stroke or transient ischaemic attack (TIA). Subjects will be analysed according to whether anticoagulant initiation was within 7 days, or after 7 days of stroke symptom onset. As this is an observational cohort study, patients undergo usual care, and the decision of when and what type of oral anticoagulant used is at the discretion of the treating clinician.
Clinical data will include: patient demographics, pre-stroke history, previous medication history, in-hospital data (baseline and 24-hour National Institute of Health Stroke Score), reperfusion treatment, antiplatelet and anticoagulant treatment post stroke, recurrent stroke and other adverse events. Follow-up information includes clinical evidence of recurrent ischaemic stroke, TIA, intracerebral haemorrhage (ICH), and the 3-month modified Rankin scale (mRS). 3-month outcomes will be recorded centrally by phone call from the coordinating centre. This includes a scripted, validated mRS assessment.

Central Review of Imaging
All imaging will be reviewed by principal investigators of the study. Investigators will be blinded to both anticoagulation type (NOAC versus warfarin) and time frame for initiation. Imaging review will follow a proforma that assesses ischaemic change as well as ICH.

Intervention type

Phase

Drug names

Primary outcome measure

New ischaemic lesions on MRI at 1 month

Secondary outcome measures

1. New clinical stroke within 90 days determined by clinic review or telephone follow up
2. Intracerebral haemorrhage on MRI at 1 month
3. Disability or dependence following stroke, assessed by mRS at 90 days determined by clinic review or telephone follow up
4. Non-intracranial bleeding within 90 days

Overall trial start date

12/06/2015

Overall trial end date

01/02/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients who present with an acute ischaemic stroke or TIA of cardioembolic (atrial fibrillation [AF]-related) origin and who have an MRI following their primary ischaemic event, and are deemed suitable for initiation of NOAC or VKA therapy
2. Subjects must be enrolled within 30 days of symptom onset

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

280

Participant exclusion criteria

1. Evidence of primary intracranial haemorrhage
2. Inability to have baseline and follow-up MRI

Recruitment start date

21/05/2016

Recruitment end date

01/11/2018

Locations

Countries of recruitment

Australia

Trial participating centre

Royal Melbourne Hospital
300 Grattan Street Parkville
Melbourne
3050
Australia

Trial participating centre

John Hunter Hospital
2305
Australia

Trial participating centre

Flinders Medical Centre
5042
Australia

Trial participating centre

Royal North Shore hospital
2065
Australia

Trial participating centre

Royal Prince Alfred Hospital
2050
Australia

Trial participating centre

Westmead Hospital
2145
Australia

Trial participating centre

Gold Coast University Hospital
4215
Australia

Trial participating centre

Princess Alexandra Hospital
4102
Australia

Trial participating centre

Royal Brisbane Hospital
4029
Australia

Trial participating centre

Calvary Wakefield Hospital
5000
Australia

Trial participating centre

Royal Adelaide Hospital
5000
Australia

Trial participating centre

The Alfred Hospital
3004
Australia

Trial participating centre

Austin Hospital
3084
Australia

Trial participating centre

Monash Medical Centre Clayon
3168
Australia

Trial participating centre

The Northern Hospital
3076
Australia

Trial participating centre

University Hospital Geelong
3220
Australia

Trial participating centre

Western Hospital
3021
Australia

Trial participating centre

Calvary Public Hospital Bruce
2617
Australia

Trial participating centre

Epworth Eastern
3128
Australia

Sponsor information

Organisation

Australasian Stroke Academy

Sponsor details

PO Box 316 Stepney South Australia 5069
South Australia
5069
Australia

Sponsor type

Research organisation

Website

Funders

Funder type

Not defined

Funder name

Andrew Lee - Chief Executive Officer of the Australasian Stroke Academy

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/02/2020

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes