Start or STop Anticoagulants Randomised Trial (SoSTART)
- Conditions
- Subdural HematomaIntraventricular HemorrhageIntracranial HemorrhagesIntracranial Hemorrhage, HypertensiveSubarachnoid HemorrhageAtrial FibrillationMicrohaemorrhageAtrial FlutterSmall Vessel Cerebrovascular Disease
- Interventions
- Registration Number
- NCT03153150
- Lead Sponsor
- University of Edinburgh
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 203
-
Patient age ≥18 years
-
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)
-
Atrial fibrillation/flutter (persistent or paroxysmal) with a CHA2DS2-VASc score ≥2
-
If included in the brain magnetic resonance imaging (MRI) sub-study, the scan must be done after symptomatic intracranial haemorrhage and before randomisation
- Symptomatic intracranial haemorrhage within the last 24 hours (when the risk of haemorrhage expansion/growth is greatest)
- Symptomatic intracranial haemorrhage is exclusively due to trauma or haemorrhagic transformation of ischaemic stroke
- Prosthetic mechanical heart valve or severe (haemodynamically significant) native valve disease
- Left atrial appendage occlusion for prevention of systemic embolism in AF done in the past, or intended to be performed
- Intention to start antiplatelet drug(s) if randomised to start full dose OAC
- Intention to start OAC or parenteral anticoagulation
- Intention to implement the allocated treatment strategy for <1 year
- Patient or their doctor is certain about whether to start or avoid full dose OAC
- Brain imaging that first diagnosed the intracranial haemorrhage is not available
- Patient is not registered with a general practitioner
- Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception
- Patient and carer unable to understand spoken or written English
- Contraindications to any of the IMPs, other than recent intracranial haemorrhage
- Contraindication to MRI (brain MRI sub-study)
- Life expectancy less than one year
- Previously randomised in SoSTART
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Start oral anticoagulant (OAC) Apixaban 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. Start oral anticoagulant (OAC) Rivaroxaban 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. Start oral anticoagulant (OAC) Edoxaban 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. Start oral anticoagulant (OAC) Acenocoumarol 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. Start oral anticoagulant (OAC) Dabigatran 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. Start oral anticoagulant (OAC) Phenindione 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. Start oral anticoagulant (OAC) Warfarin 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.
- Primary Outcome Measures
Name Time Method Recurrent symptomatic spontaneous intracranial haemorrhage (in the safety phase of the trial) 1 year after randomisation \~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.
The number of participants recruited per site per month (in the pilot phase of the trial) 1 year after trial initiation 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.
- Secondary Outcome Measures
Name Time Method 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) 1 year after randomisation The acceptability of the trial protocol to investigators and patients.
Trial Locations
- Locations (67)
Frimley Park Hospital
🇬🇧Frimley, United Kingdom
Gloucestershire Royal Hospital
🇬🇧Gloucester, United Kingdom
Pinderfields Hospital
🇬🇧Wakefield, United Kingdom
York Hospital
🇬🇧York, United Kingdom
Edinburgh Royal Infirmary
🇬🇧Edinburgh, Midlothian, United Kingdom
Nevill Hall Hospital
🇬🇧Abergavenny, United Kingdom
Monklands Hospital
🇬🇧Airdrie, United Kingdom
Barnet Hospital
🇬🇧Barnet, United Kingdom
Royal United Hospital
🇬🇧Bath, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, United Kingdom
The Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
University Hospital Bristol
🇬🇧Bristol, United Kingdom
University Hospital of Wales/ /University Hospital Llandough
🇬🇧Cardiff, United Kingdom
Altnagelvin Hospital
🇬🇧Derry, United Kingdom
Colchester General Hospital
🇬🇧Colchester, United Kingdom
Derby Royal Hospital
🇬🇧Derby, United Kingdom
University Hospital North Durham
🇬🇧Durham, United Kingdom
Royal Devon & Exeter Hospital
🇬🇧Exeter, United Kingdom
South West Acute Hospital
🇬🇧Enniskillen, 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
Calderdale Royal Hospital
🇬🇧Halifax, United Kingdom
Northwick Park
🇬🇧Harrow, United Kingdom
Ystrad Mynach Hospital
🇬🇧Hengoed, United Kingdom
Victoria Hospital Kirkcaldy
🇬🇧Kirkcaldy, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
The Royal London Hospital
🇬🇧London, United Kingdom
Royal Lancaster Infirmary
🇬🇧Lancaster, United Kingdom
Royal Liverpool and Broadgreen University Hospital
🇬🇧Liverpool, United Kingdom
Homerton University Hospital
🇬🇧London, United Kingdom
University Hospital Aintree
🇬🇧Liverpool, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
St Thomas Hospital
🇬🇧London, United Kingdom
North Middlesex University Hospital
🇬🇧London, United Kingdom
King's Mill Hospital
🇬🇧Mansfield, United Kingdom
Luton & Dunstable University Hospital
🇬🇧Luton, United Kingdom
St.George's Hospital
🇬🇧London, United Kingdom
Poole Hospital
🇬🇧Poole, United Kingdom
James Cook University Hospital
🇬🇧Middlesbrough, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle Upon Tyne, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Peterborough City Hospital
🇬🇧Peterborough, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Queen' Hospital Romford
🇬🇧Romford, United Kingdom
Royal Berkshire Hospital
🇬🇧Reading, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
University Hospital of North Tees
🇬🇧Stockton-on-Tees, United Kingdom
Morriston Hospital
🇬🇧Swansea, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, United Kingdom
The Princess Royal Hospital
🇬🇧Telford, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Torbay District General Hospital
🇬🇧Torquay, United Kingdom
Hillingdon Hospital
🇬🇧Uxbridge, United Kingdom
Southend University Hospital NHS Foundation Trust
🇬🇧Westcliff-on-Sea, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Royal Hampshire County Hospital
🇬🇧Winchester, United Kingdom
Arrowe Park Hospital
🇬🇧Wirral, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, United Kingdom