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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03153150
Recruitment Status : Active, not recruiting
First Posted : May 15, 2017
Last Update Posted : June 4, 2020
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 safety 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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 203 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 : February 28, 2021
Estimated Study Completion Date : February 28, 2021

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. Recurrent symptomatic spontaneous intracranial haemorrhage (in the safety phase of the trial) [ Time Frame: 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.


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.


Other Outcome Measures:
  1. The number of Symptomatic serious vascular events: (in the safety phase of the trial) [ Time Frame: 1 year after randomisation ]
    • 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.

  2. The number of Individual symptomatic vascular events: (in the safety phase of the trial) [ Time Frame: 1 year after randomisation ]
    • 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

  3. Annual ratings of participant dependence completed by participant, their carer or nominated contact, or healthcare provider (e.g. general practitioner): [ Time Frame: 1 year after randomisation ]
    • Simplified modified Rankin Scale

  4. Ratings of participant quality of life completed by participant, their carer or or nominated contact [ Time Frame: Randomisation and 1 year after randomisation ]
    • The 5-level EQ-5D version (EQ-5D-5L) of the EuroQol



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. 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

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


Locations
Show Show 67 study locations
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
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Principal Investigator: Rustam Al-Shahi Salman, MA PhD FRCP University of Edinburgh
Additional Information:
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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03153150    
Other Study ID Numbers: SoSTART2016
2016-004121-16 ( EudraCT Number )
First Posted: May 15, 2017    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020
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

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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:
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Subarachnoid Hemorrhage
Intracranial Hemorrhages
Cerebrovascular Disorders
Hematoma, Subdural
Intracranial Hemorrhage, Hypertensive
Cerebral Small Vessel Diseases
Atrial Fibrillation
Atrial Flutter
Hemorrhage
Hematoma
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
Warfarin
Rivaroxaban
Dabigatran
Apixaban
Edoxaban
Acenocoumarol
Phenindione
Anticoagulants