Start or STop Anticoagulants Randomised Trial (SoSTART)

Atrial Fibrillation Clinical Trial

— SoSTART  

Official title:

Start or STop Anticoagulants Randomised Trial (SoSTART) After Spontaneous Intracranial Haemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03153150
• Other study ID #: SoSTART2016
• Secondary ID: 2016-004121-16
• Status: Completed
• Phase: Phase 3
• Start date: March 28, 2018
• Est. completion date: March 26, 2021

Study information

• Verified date: May 2021
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary research question: For adults surviving spontaneous (non-traumatic) symptomatic intracranial haemorrhage with persistent/paroxysmal atrial fibrillation/flutter (AF), does starting full treatment dose oral anticoagulation (OAC) result in a beneficial net reduction of all serious vascular events compared with not starting OAC?

Trial design: Investigator-led, multicentre, randomised, open, assessor-masked, parallel group, clinical trial of investigational medicinal product (CTIMP) prescribing strategies. Investigators plan for a pilot phase, followed by a safety phase.

Description:

Bleeding within the skull, also known as brain haemorrhage, affects 3 million people in the world each year.

One in five people who survive brain haemorrhage have an irregular heart rhythm called 'atrial fibrillation', which puts them at risk of stroke and other blood clots.

Blood-thinning medicines, known as 'anticoagulant' drugs, are used in everyday clinical practice to protect people with atrial fibrillation from developing blood clots. However, these drugs also increase the risk of bleeding and are usually stopped when the brain haemorrhage occurs.

But when patients recover from brain haemorrhage, they and their doctors are often uncertain about whether to start or stop these drugs to prevent further clots occurring, or whether to avoid them in case they increase the risk of brain haemorrhage happening again.

Investigators want to find out whether starting or not starting an anticoagulant drugs is better for those patients.

A network of hospital doctors, nurses, and other staff will identify people who survive brain haemorrhage and have atrial fibrillation. If a patient and their doctor are uncertain about whether to start an anticoagulant drug, they may invite the patient to participate.

In the pilot phase, investigators aim to recruit at least 60 participants to determine the feasibility of recruiting the target sample size of at least 190 participants in the safety phase of the trial.

Investigators will follow-up all participants for at least one year to determine whether prescribing an anticoagulant drug reduces the occurrence of all serious vascular events like heart attack, stroke compared with a policy of avoiding oral anticoagulant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: March 26, 2021
• Est. primary completion date: March 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient age =18 years

2. Symptomatic intracranial haemorrhage (i.e. intracerebral haemorrhage, non-aneurysmal subarachnoid haemorrhage,intraventricular haemorrhage, or subduralhaemorrhage)

• Not attributable to a known underlying intracranial aneurysm, arteriovenous malformation, cerebral cavernous malformation, dural arteriovenous fistula, intracranial venous thrombosis

• Not attributable to known head injury, based on:

• a history from the patient/witness of spontaneous symptom onset without preceding head trauma (head trauma occurring after symptom onset is permissible)

• brain imaging appearances consistent with spontaneous intracranial haemorrhage (which may be accompanied by the brain/bone/soft tissue appearances of trauma occurring subsequently)

3. Atrial fibrillation/flutter (persistent or paroxysmal) with a CHA2DS2-VASc score =2

4. If included in the brain magnetic resonance imaging (MRI) sub-study, the scan must be done after symptomatic intracranial haemorrhage and before randomisation

Exclusion Criteria:

1. Symptomatic intracranial haemorrhage within the last 24 hours (when the risk of haemorrhage expansion/growth is greatest)

2. Symptomatic intracranial haemorrhage is exclusively due to trauma or haemorrhagic transformation of ischaemic stroke

3. Prosthetic mechanical heart valve or severe (haemodynamically significant) native valve disease

4. Left atrial appendage occlusion for prevention of systemic embolism in AF done in the past, or intended to be performed

5. Intention to start antiplatelet drug(s) if randomised to start full dose OAC

6. Intention to start OAC or parenteral anticoagulation

7. Intention to implement the allocated treatment strategy for <1 year

8. Patient or their doctor is certain about whether to start or avoid full dose OAC

9. Brain imaging that first diagnosed the intracranial haemorrhage is not available

10. Patient is not registered with a general practitioner

11. Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception

12. Patient and carer unable to understand spoken or written English

13. Contraindications to any of the IMPs, other than recent intracranial haemorrhage

14. Contraindication to MRI (brain MRI sub-study)

15. Life expectancy less than one year

16. Previously randomised in SoSTART

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Flutter
• Cerebral Small Vessel Diseases
• Cerebrovascular Disorders
• Hematoma
• Hemorrhage
• Intracranial Hemorrhage, Hypertensive
• Intracranial Hemorrhages
• Intraventricular Hemorrhage
• Microhaemorrhage
• Small Vessel Cerebrovascular Disease
• Subarachnoid Hemorrhage
• Subdural Hematoma

Intervention

Drug:
• Apixaban
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
• Rivaroxaban
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
• Edoxaban
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
• Dabigatran
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
• Acenocoumarol
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
• Phenindione
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
• Warfarin
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Nevill Hall Hospital	Abergavenny
United Kingdom	Monklands Hospital	Airdrie
United Kingdom	Barnet Hospital	Barnet
United Kingdom	Royal United Hospital	Bath
United Kingdom	Heartlands Hospital	Birmingham
United Kingdom	The Royal Bournemouth Hospital	Bournemouth
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	University Hospital Bristol	Bristol
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	University Hospital of Wales/ /University Hospital Llandough	Cardiff
United Kingdom	Colchester General Hospital	Colchester
United Kingdom	Derby Royal Hospital	Derby
United Kingdom	Altnagelvin Hospital	Derry
United Kingdom	University Hospital North Durham	Durham
United Kingdom	Edinburgh Royal Infirmary	Edinburgh	Midlothian
United Kingdom	South West Acute Hospital	Enniskillen
United Kingdom	Royal Devon & Exeter Hospital	Exeter
United Kingdom	Frimley Park Hospital	Frimley
United Kingdom	Queen Elizabeth Hospital	Gateshead
United Kingdom	Medway Maritime Hospital	Gillingham
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Gloucestershire Royal Hospital	Gloucester
United Kingdom	Calderdale Royal Hospital	Halifax
United Kingdom	Northwick Park	Harrow
United Kingdom	Ystrad Mynach Hospital	Hengoed
United Kingdom	Victoria Hospital Kirkcaldy	Kirkcaldy
United Kingdom	Royal Lancaster Infirmary	Lancaster
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Royal Liverpool and Broadgreen University Hospital	Liverpool
United Kingdom	University Hospital Aintree	Liverpool
United Kingdom	Homerton University Hospital	London
United Kingdom	North Middlesex University Hospital	London
United Kingdom	St Thomas Hospital	London
United Kingdom	St.George's Hospital	London
United Kingdom	The Royal London Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	Luton & Dunstable University Hospital	Luton
United Kingdom	King's Mill Hospital	Mansfield
United Kingdom	James Cook University Hospital	Middlesbrough
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Poole Hospital	Poole
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Royal Berkshire Hospital	Reading
United Kingdom	Queen' Hospital Romford	Romford
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United Kingdom	Royal Hallamshire Hospital	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	University Hospital of North Tees	Stockton-on-Tees
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent
United Kingdom	Sunderland Royal Hospital	Sunderland
United Kingdom	Morriston Hospital	Swansea
United Kingdom	The Princess Royal Hospital	Telford
United Kingdom	Torbay District General Hospital	Torquay
United Kingdom	Royal Cornwall Hospital	Truro
United Kingdom	Hillingdon Hospital	Uxbridge
United Kingdom	Pinderfields Hospital	Wakefield
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-on-Sea
United Kingdom	Royal Hampshire County Hospital	Winchester
United Kingdom	Arrowe Park Hospital	Wirral
United Kingdom	New Cross Hospital	Wolverhampton
United Kingdom	Yeovil District Hospital	Yeovil
United Kingdom	York Hospital	York

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

SoSTART Collaboration. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial. Lancet Neurol. 2021 Oct;20(10):842-853. doi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The number of Symptomatic serious vascular events: (in the safety phase of the trial)	• All symptomatic serious vascular events (i.e. major adverse cardiac or cerebrovascular events [MACCE]) including: non-fatal (i.e. not followed by death within 30 days of onset) myocardial infarction; stroke (i.e. ischaemic, haemorrhagic, unknown sub-type) or spontaneous subdural haemorrhage; or death from a vascular cause (i.e. haemorrhagic or ischaemic events followed by death within 30 days), sudden death, or death of an unknown cause.	1 year after randomisation
Other	The number of Individual symptomatic vascular events: (in the safety phase of the trial)	Major haemorrhagic events (Bleeding Academic Research Consortium types 3-5); Recurrent symptomatic spontaneous intracranial haemorrhage; Extracranial haemorrhage; Symptomatic ischaemic events; ischaemic stroke; myocardial infarction; peripheral arterial occlusion; mesenteric ischaemia; central retinal arterial occlusion; deep vein thrombosis; pulmonary embolism; cardiac death with symptoms suggestive of myocardial ischaemia (type 3),or evidence of arrhythmia; Revascularisation procedures (carotid, coronary, or peripheral arterial); Symptomatic stroke of uncertain sub-type; Non-fatal stroke, with brain imaging performed too late to distinguish haemorrhage from infarction; Rapidly fatal stroke, but without radiographic or pathological confirmation	1 year after randomisation
Other	Annual ratings of participant dependence completed by participant, their carer or nominated contact, or healthcare provider (e.g. general practitioner):	• Simplified modified Rankin Scale	1 year after randomisation
Other	Ratings of participant quality of life completed by participant, their carer or or nominated contact	• The 5-level EQ-5D version (EQ-5D-5L) of the EuroQol	Randomisation and 1 year after randomisation
Primary	The number of participants recruited per site per month (in the pilot phase of the trial)	The rate of recruiting up to 60 participants to determine the feasibility of recruiting the target sample size in the main phase of the trial in an acceptable timescale.	1 year after trial initiation
Primary	Recurrent symptomatic spontaneous intracranial haemorrhage (in the safety phase of the trial)	~60 hospital sites will recruit at least 190 participants to determine whether the risk of recurrent symptomatic intracranial haemorrhage is sufficiently low (non-inferior) to justify a definitive trial.	1 year after randomisation
Secondary	The proportions of all eligible patients recorded on screening logs who are recruited, unsuitable, or decline to participate (in the pilot phase of the trial)	The acceptability of the trial protocol to investigators and patients.	1 year after randomisation

External Links

•   Chief investigator details
•   Trial website