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Clinical Relevance of Microbleeds In Stroke (CROMIS-2)

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: NCT02513316
Recruitment Status : Completed
First Posted : July 31, 2015
Last Update Posted : November 17, 2017
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief Summary:

Study I: CROMIS-2 (AF) Prospective cohort study of patients anticoagulated after cardioembolic stroke An observational inception cohort study (n=1425) of patients throughout the United Kingdom (UK) - (79 hospitals) started on best practice oral anticoagulant (without prior use) for presumed cardioembolic ischaemic stroke due to non-valvular AF with follow up for the occurrence of intracerebral haemorrhage (ICH) and ischaemic stroke for an average of two years. The main baseline exposures (risk factors of interest) are the presence of cerebral microbleeds (CMBs) on magnetic resonance imaging (MRI), and genetic polymorphisms in candidate genes with potential functional relevance to ICH risk.

Study II: CROMIS-2 (ICH) Observational and genetics study of intracerebral haemorrhage The investigators will also recruit 600 patients admitted to participating centres with ICH (with a target of at least 300 anticoagulant-related ICH cases) and collect DNA to increase the power of the genetic studies. The investigators will collect clinical and imaging data from these ICH cases to investigate risk factors associated with anticoagulant-related ICH compared to non anticoagulant-related ICH.


Condition or disease
Stroke Atrial Fibrillation (AF) Intracerebral Haemorrhage (ICH)

Detailed Description:

Background Over the last decade, increasing use of oral anticoagulants to prevent cardioembolic ischaemic stroke due to atrial fibrillation (AF) in an ageing population has led to a five-fold increase in the incidence of anticoagulant-related intracranial haemorrhage (ICH) - a rare but unpredictable and catastrophic complication. Cerebral microbleeds (CMBs) on magnetic resonance imaging (MRI) may predict ICH risk, as may genetic polymorphisms influencing brain small-vessel integrity or anticoagulation stability.

Aims To establish the value of CMBs and genetic factors in predicting symptomatic ICH following best practice oral anticoagulation to prevent recurrent ischaemic stroke due to AF.

Methods CROMIS-2: Study I (AF) - Prospective, multicentre, inception cohort study in 1425 patients with ischaemic stroke due to AF started on best practice oral anticoagulation. Patients will have genetic testing and standardized MRI including Gradient recalled Echo (GRE) at baseline, with follow-up by postal questionnaire (and clinical assessment or medical records surveillance after suspected events), and where possible there will be an in person clinical assessment at 2 years. The investigators will compare the rate of symptomatic ICH between CMB and CMB-free patients and test for associations with plausible candidate genes. The investigators aim to develop and validate a risk model to predict symptomatic ICH following best practice oral anticoagulation to prevent recurrent ischaemic stroke due to AF.

CROMIS-2: Study II (ICH) - An observational study of ICH investigating genetic, clinical and radiological risk factors associated with anticoagulant-related ICH. The investigators will recruit patients admitted to participating centres with ICH (with a target of at least 300 anticoagulant-related ICH cases) and collect DNA to increase the power of the genetic studies. The investigators will collect clinical and imaging data from these ICH cases to investigate risk factors associated with anticoagulant-related ICH compared to non anticoagulant-related ICH.

Expected outcomes A successful predictive model for ICH risk after best practice oral anticoagulation for AF will help to determine whether genetic or CMB screening should be used in clinical practice and future trials. New genetic, clinical and radiological risk factors associated with anticoagulant-related ICH will be identified.

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Study Type : Observational
Actual Enrollment : 2490 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Microbleeds and Genetic Risk Factors to Predict the Risk of Intracranial Haemorrhage in Patients Treated With Anticoagulation Following Cardioembolic Stroke Due to Atrial Fibrillation
Actual Study Start Date : August 4, 2011
Actual Primary Completion Date : July 31, 2017
Actual Study Completion Date : October 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Group/Cohort
Study I (AF)
Prospective cohort study of patients anticoagulated after cardioembolic stroke started on best practice oral anticoagulant (without prior use) for presumed cardioembolic ischaemic stroke due to non-valvular AF with follow up for the occurrence of ICH, ischaemic stroke and cognitive function for an average of two years. Our main baseline exposures (risk factors of interest) are the presence of CMBs on MRI, and genetic polymorphisms in candidate genes with potential functional relevance to ICH risk.
Study II (ICH)
Observational and genetics study of intracerebral haemorrhage Patients with ICH (non anticoagulant-related ICH cases and anticoagulant-related ICH cases).



Primary Outcome Measures :
  1. Symptomatic intracranial haemorrhage [ Time Frame: 24 months ]

    Symptomatic intracranial haemorrhage (confirmed on brain imaging). Intracranial haemorrhage includes any bleeding within the skull, regardless of the site. The investigators will record the incidence of different haemorrhage subtypes (intracerebral, subdural, extradural, subarachnoid).

    This will be assessed using hospital records, General Practitioner (GP) follow up and National Health Service (NHS) information data system.



Secondary Outcome Measures :
  1. Ischaemic stroke [ Time Frame: 24 months ]
    Patient experiencing an ischaemic stroke during 2 year follow up.This will be assessed using hospital records, General Practitioner (GP) follow up and National Health Service (NHS) information data system.

  2. Transient Ischaemic Attack (TIA) [ Time Frame: 24 months ]
    Patient experiencing a TIA after recruitment during 2 year follow up.This will be assessed using hospital records, General Practitioner (GP) follow up and National Health Service (NHS) information data system.

  3. Death [ Time Frame: 24 months ]
    Patient death (of any cause). Assessed by General Practitioner (GP) follow up, recruiting hospital records and National Health Service (NHS) Information Centre data systems.

  4. Any other major haemorrhagic events other than ICH [ Time Frame: 24 months ]
    Prolonged epistaxis, cutaneous bruising, gastrointestinal bleeding, haematuria, muscle haematoma, haemarthrosis. Assessed by General Practitioner (GP) follow up, recruiting hospital records and National Health Service (NHS) Information Centre data systems.

  5. Long term physical disability [ Time Frame: 24 months ]
    Assessed by administering Modified Rankin Score (mRS) to patients at 6,12 and 24 months via patient questionnaire.


Biospecimen Retention:   Samples With DNA
Blood samples


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
Sampling Method:   Non-Probability Sample
Study Population

Study I: CROMIS-2 (AF) Prospective cohort study of patients anticoagulated after cardioembolic stroke Study I (AF): 1425 patients from UK centres. All eligible patients with first or recurrent ischaemic stroke and TIA in whom it is decided that best practice oral anticoagulant treatment is to be commenced.

Study II (ICH): The investigators will recruit 600 patients treated at participating hospitals with ICH. Of these patients, 300 ICH cases will be related to anticoagulant use. The investigators will also recruit at least 300 ICH cases not related to anticoagulant use during the study period. Patients seen in outpatient clinics or from existing databases may also be recruited, at centres where these are available.

Criteria

Study I: CROMIS-2 (AF)

Inclusion criteria:

  • Adult (≥18y; no upper limit) patients with a clinical diagnosis of non-valvular AF (verified by ECG) with intention to treat with best practice oral anticoagulants (e.g. warfarin)
  • Previous ischaemic stroke or TIA diagnosed by treating clinician
  • All patients must be able to have GRE MRI before (or within 1 week) of starting best practice oral anticoagulant

Exclusion Criteria:

  • Any MRI contraindications
  • Previous use of oral anticoagulation
  • Definite contra-indication to oral anticoagulation
  • Serious head injury (resulting to loss of consciousness)

Study II: CROMIS-2 (ICH)

Inclusion criteria:

• Adult (>18y) patients treated at participating centres with confirmed ICH (confirmed on CT or MRI scans) with or without a history of anticoagulant use at the time of the ICH

Exclusion criteria:

  • Known underlying structural cause for ICH (e.g arteriovenous malformation, tumour, cavernoma, intracranial aneurysm, haemorrhagic transformation of an infarct)
  • Major head trauma (causing loss of consciousness and though to be sufficient to have caused the ICH) in previous 24 hours

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): NCT02513316


Locations
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United Kingdom
UCL
London, United Kingdom, WC1N 3BG
Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: David Werring UCL
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02513316    
Other Study ID Numbers: 11/0116
First Posted: July 31, 2015    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: October 2017
Keywords provided by University College, London:
Microbleeds
Additional relevant MeSH terms:
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Stroke
Cerebral Hemorrhage
Atrial Fibrillation
Hemorrhage
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Intracranial Hemorrhages