Start or STop Anticoagulants Randomised Trial (SoSTART)

NCT ID: NCT03153150

Last Updated: 2022-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

203 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-28

Study Completion Date

2021-03-26

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

1:1 allocation of intervention: comparator, using a minimisation algorithm
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
PROBE design

Study Groups

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Start oral anticoagulant (OAC)

If the patient is randomized in this arm, an oral anticoagulant:

* Factor Xa inhibitors: Apixaban or Rivaroxaban or Edoxaban or
* Direct thrombin inhibitor: Dabigatran or
* Vitamin K antagonists: Acenocoumarol or Phenindione or Warfarin chosen by the patient's physician before the randomisation, will be prescribed long-term (≥1 year) to the patient.

Group Type EXPERIMENTAL

Apixaban

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Rivaroxaban

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Edoxaban

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Dabigatran

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Acenocoumarol

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Phenindione

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Warfarin

Intervention Type DRUG

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Do not start oral anticoagulant (OAC)

If the patient is randomized in this arm, anticoagulant drugs will not be prescribed to the patient during the entire study period. The standard clinical practice without OAC may include:

* antiplatelet drug(s) or
* no antithrombotic drugs.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Apixaban

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Rivaroxaban

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Edoxaban

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Dabigatran

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Acenocoumarol

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Phenindione

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Warfarin

The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.

Intervention Type DRUG

Other Intervention Names

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Eliquis Xarelto Lixiana Pradaxa Sinthrome Dindevan Marevan Coumadin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NHS Lothian

OTHER_GOV

Sponsor Role collaborator

University of Edinburgh

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rustam Al-Shahi Salman, MA PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

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Edinburgh Royal Infirmary

Edinburgh, Midlothian, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

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Nevill Hall Hospital

Abergavenny, , United Kingdom

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Monklands Hospital

Airdrie, , United Kingdom

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Barnet Hospital

Barnet, , United Kingdom

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Royal United Hospital

Bath, , United Kingdom

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Heartlands Hospital

Birmingham, , United Kingdom

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The Royal Bournemouth Hospital

Bournemouth, , United Kingdom

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Bradford Royal Infirmary

Bradford, , United Kingdom

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University Hospital Bristol

Bristol, , United Kingdom

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Addenbrookes Hospital

Cambridge, , United Kingdom

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University Hospital of Wales/ /University Hospital Llandough

Cardiff, , United Kingdom

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Colchester General Hospital

Colchester, , United Kingdom

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Derby Royal Hospital

Derby, , United Kingdom

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University Hospital North Durham

Durham, , United Kingdom

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South West Acute Hospital

Enniskillen, , United Kingdom

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Royal Devon & Exeter Hospital

Exeter, , United Kingdom

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Frimley Park Hospital

Frimley, , United Kingdom

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Queen Elizabeth Hospital

Gateshead, , United Kingdom

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Medway Maritime Hospital

Gillingham, , United Kingdom

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Glasgow Royal Infirmary

Glasgow, , United Kingdom

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Queen Elizabeth University Hospital

Glasgow, , United Kingdom

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Gloucestershire Royal Hospital

Gloucester, , United Kingdom

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Calderdale Royal Hospital

Halifax, , United Kingdom

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Northwick Park

Harrow, , United Kingdom

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Ystrad Mynach Hospital

Hengoed, , United Kingdom

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Victoria Hospital Kirkcaldy

Kirkcaldy, , United Kingdom

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Royal Lancaster Infirmary

Lancaster, , United Kingdom

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Leeds General Infirmary

Leeds, , United Kingdom

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Royal Liverpool and Broadgreen University Hospital

Liverpool, , United Kingdom

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University Hospital Aintree

Liverpool, , United Kingdom

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The Royal London Hospital

London, , United Kingdom

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Homerton University Hospital

London, , United Kingdom

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North Middlesex University Hospital

London, , United Kingdom

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University College London Hospital

London, , United Kingdom

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St Thomas Hospital

London, , United Kingdom

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St.George's Hospital

London, , United Kingdom

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Altnagelvin Hospital

Londonderry, , United Kingdom

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Luton & Dunstable University Hospital

Luton, , United Kingdom

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King's Mill Hospital

Mansfield, , United Kingdom

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Arrowe Park Hospital

Metropolitan Borough of Wirral, , United Kingdom

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James Cook University Hospital

Middlesbrough, , United Kingdom

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Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

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Nottingham City Hospital

Nottingham, , United Kingdom

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John Radcliffe Hospital

Oxford, , United Kingdom

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Peterborough City Hospital

Peterborough, , United Kingdom

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Poole Hospital

Poole, , United Kingdom

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Royal Preston Hospital

Preston, , United Kingdom

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Royal Berkshire Hospital

Reading, , United Kingdom

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Queen' Hospital Romford

Romford, , United Kingdom

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Salford Royal NHS Foundation Trust

Salford, , United Kingdom

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Royal Hallamshire Hospital

Sheffield, , United Kingdom

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Southampton General Hospital

Southampton, , United Kingdom

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University Hospital of North Tees

Stockton-on-Tees, , United Kingdom

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Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

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Sunderland Royal Hospital

Sunderland, , United Kingdom

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Morriston Hospital

Swansea, , United Kingdom

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The Princess Royal Hospital

Telford, , United Kingdom

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Torbay District General Hospital

Torquay, , United Kingdom

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Royal Cornwall Hospital

Truro, , United Kingdom

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Hillingdon Hospital

Uxbridge, , United Kingdom

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Pinderfields Hospital

Wakefield, , United Kingdom

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Southend University Hospital NHS Foundation Trust

Westcliff-on-Sea, , United Kingdom

Site Status

Royal Hampshire County Hospital

Winchester, , United Kingdom

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New Cross Hospital

Wolverhampton, , United Kingdom

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Yeovil District Hospital

Yeovil, , United Kingdom

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York Hospital

York, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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: 10.1016/S1474-4422(21)00264-7. Epub 2021 Sep 3.

Reference Type RESULT
PMID: 34487722 (View on PubMed)

Cochrane A, Chen C, Stephen J, Ronning OM, Anderson CS, Hankey GJ, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD012144. doi: 10.1002/14651858.CD012144.pub3.

Reference Type DERIVED
PMID: 36700520 (View on PubMed)

Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2.

Reference Type DERIVED
PMID: 34022170 (View on PubMed)

Related Links

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http://www.rush.ed.ac.uk

Chief investigator details

Other Identifiers

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2016-004121-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SoSTART2016

Identifier Type: -

Identifier Source: org_study_id

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