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Start or STop Anticoagulants Randomised Trial (SoSTART) (SoSTART)

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ClinicalTrials.gov Identifier: NCT03153150
Recruitment Status : Recruiting
First Posted : May 15, 2017
Last Update Posted : June 28, 2018
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
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 main phase.


Condition or disease Intervention/treatment Phase
Intracranial Hemorrhages Intracranial Hemorrhage, Hypertensive Subarachnoid Hemorrhage Subdural Hematoma Intraventricular Hemorrhage Atrial Fibrillation Atrial Flutter Small Vessel Cerebrovascular Disease Microhaemorrhage Drug: Apixaban Drug: Rivaroxaban Drug: Edoxaban Drug: Dabigatran Drug: Acenocoumarol Drug: Phenindione Drug: Warfarin Phase 3

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 800 participants in the main 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1:1 allocation of intervention: comparator, using a minimisation algorithm
Masking: Single (Outcomes Assessor)
Masking Description: PROBE design
Primary Purpose: Prevention
Official Title: Start or STop Anticoagulants Randomised Trial (SoSTART) After Spontaneous Intracranial Haemorrhage
Actual Study Start Date : March 28, 2018
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Apixaban
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Name: Eliquis

Drug: Rivaroxaban
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Name: Xarelto

Drug: Edoxaban
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Name: Lixiana

Drug: Dabigatran
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Name: Pradaxa

Drug: Acenocoumarol
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Name: Sinthrome

Drug: Phenindione
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Name: Dindevan

Drug: Warfarin
The participant will be allocated to start this oral anticoagulant drug, if the participant's doctor indicated it before randomisation.
Other Names:
  • Marevan
  • Coumadin

No Intervention: 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.



Primary Outcome Measures :
  1. The number of participants recruited per site per month (in the pilot phase of the trial) [ Time Frame: 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.

  2. The incidence rate of the first occurrence of the composite outcome of all symptomatic serious vascular events (in the main phase of the trial) [ Time Frame: 1 year after randomisation ]

    The composite outcome will comprise:

    • Non-fatal acute coronary syndrome (i.e. not followed by death within 30 days of onset)
    • Non-fatal stroke (i.e. ischaemic, haemorrhagic or unknown sub-type, not followed by death within 30 days of onset)
    • 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.


Secondary Outcome Measures :
  1. 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) [ Time Frame: 1 year after randomisation ]
    The acceptability of the trial protocol to investigators and patients.

  2. The incidence rate of the first occurrence of each individual symptomatic serious vascular event type (in the main phase of the trial) [ Time Frame: 1 year after randomisation ]

    Major haemorrhagic events:

    • Fatal bleeding, and/or
    • Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or
    • Bleeding causing a fall in haemoglobin level of 20 g/l (1.24 mmol/l) or more, or leading to transfusion of two or more units of whole blood or red cells

    Symptomatic ischaemic events:

    • transient ischaemic attack
    • ischaemic stroke
    • acute coronary syndrome
    • peripheral arterial occlusion/insufficiency
    • mesenteric ischaemia
    • 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

    Individual types of fatal events


  3. The proportion of participants in each category of death or dependence on the modified Rankin Scale (in the main phase of the trial) [ Time Frame: 1 year after randomisation ]
    modified Rankin Scale score, collected using structured questions, completed by the participant, their carer or a nominated contact



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient age ≥18 years
  2. 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 intracranial haemorrhage and before randomisation

Exclusion Criteria:

  1. Intracranial haemorrhage within the last 24 hours (when the risk of haemorrhage expansion/growth is greatest)
  2. 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. Intention to perform left atrial appendage occlusion for prevention of systemic embolism in AF
  5. Intention to start antiplatelet drug(s) if randomised to start full dose OAC
  6. Intention to start OAC if randomised to either start antiplatelet drugs or avoid all antithrombotic drugs
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03153150


Contacts
Contact: Rustam Al-Shahi Salman, MA PhD FRCP (0044) 0131 465 9602 rustam.al-shahi@ed.ac.uk
Contact: Kasia Adamczuk, MSc (0044) 0131 465 9592 Kasia.Adamczuk@ed.ac.uk

Locations
United Kingdom
Edinburgh Royal Infirmary Recruiting
Edinburgh, Midlothian, United Kingdom, EH16 4SB
Contact: Rustam Al-Shahi Salman, MA PhD FRCP         
Aberdeen Royal Infirmary Not yet recruiting
Aberdeen, United Kingdom, AB25 2ZN
Contact: Mary Joan MacLeod         
Nevill Hall Hospital Not yet recruiting
Abergavenny, United Kingdom, NP7 7EG
Contact: Bella Richard         
Monklands Hospital Recruiting
Airdrie, United Kingdom, ML6 0JS
Contact: Mark Baber         
Barnet Hospital Not yet recruiting
Barnet, United Kingdom, EN5 3DJ
Contact: Sam Qureshi         
Royal United Hospital Recruiting
Bath, United Kingdom, BA1 3NG
Contact: James Choulerton         
Bradford Royal Infirmary Recruiting
Bradford, United Kingdom, BD9 6RJ
Contact: Hawraman Ramadan         
University Hospital Bristol Recruiting
Bristol, United Kingdom, BS2 8HW
Contact: Clare Holmes         
Altnagelvin Hospital Not yet recruiting
Derry, United Kingdom, BT47 6SB
Contact: Mark McCarron         
Doncaster Royal Infirmary Not yet recruiting
Doncaster, United Kingdom, DN2 5LT
Contact: Manohar Kini         
Royal Devon & Exeter Hospital Recruiting
Exeter, United Kingdom, EX2 5DW
Contact: Paul Mudd         
Queen Elizabeth University Hospital Recruiting
Glasgow, United Kingdom, G51 4TF
Contact: Keith Muir         
Calderdale Royal Hospital Recruiting
Halifax, United Kingdom, HX3 0PW
Contact: Anand Nair         
Northwick Park Recruiting
Harrow, United Kingdom, HA1 3UJ
Contact: David Cohen         
Victoria Hospital Kirkcaldy Recruiting
Kirkcaldy, United Kingdom, KY2 5AH
Contact: Vera Cvoro         
Leeds General Infirmary Not yet recruiting
Leeds, United Kingdom, LS13EX
Contact: Vasileios Papavasileiou         
North Middlesex University Hospital Not yet recruiting
London, United Kingdom, N18 1QX
Contact: Robert Luder         
University College London Hospital Recruiting
London, United Kingdom, NW1 2BU
Contact: David Werring         
St Thomas Hospital Recruiting
London, United Kingdom, SE1 7EH
Contact: Anthony Rudd         
St.George's Hospital Not yet recruiting
London, United Kingdom, SW17 OQT
Contact: Gilian Cluckie         
James Cook University Hospital Not yet recruiting
Middlesbrough, United Kingdom, TS4 3BW
Contact: Samer Al-Hussayni         
Nottingham City Hospital Recruiting
Nottingham, United Kingdom, NG5 1PB
Contact: Senthil Raghunathan         
Queen Alexandra Hospital Not yet recruiting
Portsmouth, United Kingdom, PO6 3LY
Contact: Shivaprasad Siddegowda         
Royal Preston Hospital Recruiting
Preston, United Kingdom, PR2 9HT
Contact: Hedley Emsley         
Salford Royal NHS Foundation Trust Recruiting
Salford, United Kingdom, M6 8HD
Contact: Adrian Parry-Jones         
Royal Hallamshire Hospital Recruiting
Sheffield, United Kingdom, S10 2JF
Contact: Kirsty Harkness         
Southampton General Hospital Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Contact: Nic Weir         
Royal Stoke University Hospital Recruiting
Stoke-on-Trent, United Kingdom, ST4 6QG
Contact: Girish Muddegowda         
Morriston Hospital Recruiting
Swansea, United Kingdom, SA6 6NL
Contact: Tal Anjum         
Torbay District General Hospital Not yet recruiting
Torquay, United Kingdom, TQ2 7AA
Contact: Biju Bhaskaran         
New Cross Hospital Not yet recruiting
Wolverhampton, United Kingdom, WV10 0QP
Contact: Ken Fotherby         
Yeovil District Hospital Recruiting
Yeovil, United Kingdom, BA21 4AT
Contact: Khalid Rashed         
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
Principal Investigator: Rustam Al-Shahi Salman, MA PhD FRCP University of Edinburgh

Additional Information:
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03153150     History of Changes
Other Study ID Numbers: SoSTART2016
2016-004121-16 ( EudraCT Number )
First Posted: May 15, 2017    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Chief Investigator (Prof. Rustam Al-Shahi Salman) has established the Collaboration Of Controlled Randomised trials of Oral Antithrombotic drugs after intraCranial Haemorrhage (COCROACH) working towards a pre-planned individual patient data meta-analysis

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Edinburgh:
Oral anticoagulant
Factor Xa inhibitors
Direct thrombin inhibitor
Vitamin K antagonist
Antiplatelet drug

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Atrial Fibrillation
Hemorrhage
Subarachnoid Hemorrhage
Hematoma
Atrial Flutter
Intracranial Hemorrhages
Cerebrovascular Disorders
Cerebral Hemorrhage
Hematoma, Subdural
Intracranial Hemorrhage, Hypertensive
Cerebral Small Vessel Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Intracranial Hemorrhage, Traumatic
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Apixaban
Edoxaban
Warfarin
Rivaroxaban
Dabigatran
Anticoagulants