Clinical trial NCT03153150: Start or STop Anticoagulants Randomised Trial (SoSTART)
Official title: Start or STop Anticoagulants Randomised Trial (SoSTART) After Spontaneous Intracranial Haemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intracranial Hemorrhages
Intracranial Hemorrhage, Hypertensive
Subarachnoid Hemorrhage
Subdural Hematoma
Intraventricular Hemorrhage
Atrial Fibrillation
Atrial Flutter
Small Vessel Cerebrovascular Disease
Microhaemorrhage
Keywords: Oral anticoagulant
Factor Xa inhibitors
Direct thrombin inhibitor
Vitamin K antagonist
Antiplatelet drug
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
First posted: 2017-05-15
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 allocation of intervention: comparator, using a minimisation algorithm
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The number of participants recruited per site per month (in the pilot phase of the trial)
timeFrame: 1 year after trial initiation
measure: Recurrent symptomatic spontaneous intracranial haemorrhage (in the safety phase of the trial)
timeFrame: 1 year after randomisation
Secondary outcomes:
measure: 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)
timeFrame: 1 year after randomisation
Other outcomes:
measure: The number of Symptomatic serious vascular events: (in the safety phase of the trial)
timeFrame: 1 year after randomisation
measure: The number of Individual symptomatic vascular events: (in the safety phase of the trial)
timeFrame: 1 year after randomisation
measure: Annual ratings of participant dependence completed by participant, their carer or nominated contact, or healthcare provider (e.g. general practitioner):
timeFrame: 1 year after randomisation
measure: Ratings of participant quality of life completed by participant, their carer or or nominated contact
timeFrame: Randomisation and 1 year after randomisation
Locations:
city: Edinburgh
country: United Kingdom
facility: Edinburgh Royal Infirmary
state: Midlothian
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Abergavenny
country: United Kingdom
facility: Nevill Hall Hospital
city: Airdrie
country: United Kingdom
facility: Monklands Hospital
city: Barnet
country: United Kingdom
facility: Barnet Hospital
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Bristol
country: United Kingdom
facility: University Hospital Bristol
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales/ /University Hospital Llandough
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
city: Derby
country: United Kingdom
facility: Derby Royal Hospital
city: Derry
country: United Kingdom
facility: Altnagelvin Hospital
city: Durham
country: United Kingdom
facility: University Hospital North Durham
city: Enniskillen
country: United Kingdom
facility: South West Acute Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: Halifax
country: United Kingdom
facility: Calderdale Royal Hospital
city: Harrow
country: United Kingdom
facility: Northwick Park
city: Hengoed
country: United Kingdom
facility: Ystrad Mynach Hospital
city: Kirkcaldy
country: United Kingdom
facility: Victoria Hospital Kirkcaldy
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen University Hospital
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: Homerton University Hospital
city: London
country: United Kingdom
facility: North Middlesex University Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: St Thomas Hospital
city: London
country: United Kingdom
facility: St.George's Hospital
city: Luton
country: United Kingdom
facility: Luton & Dunstable University Hospital
city: Mansfield
country: United Kingdom
facility: King's Mill Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
city: Romford
country: United Kingdom
facility: Queen' Hospital Romford
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Stockton-on-Tees
country: United Kingdom
facility: University Hospital of North Tees
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
city: Telford
country: United Kingdom
facility: The Princess Royal Hospital
city: Torquay
country: United Kingdom
facility: Torbay District General Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital
city: Wakefield
country: United Kingdom
facility: Pinderfields Hospital
city: Westcliff-on-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
city: Winchester
country: United Kingdom
facility: Royal Hampshire County Hospital
city: Wirral
country: United Kingdom
facility: Arrowe Park Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
city: York
country: United Kingdom
facility: York Hospital
Study officials:
affiliation: University of Edinburgh
name: Rustam Al-Shahi Salman, MA PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.