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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

Tracking Information
First Submitted Date July 29, 2015
First Posted Date July 31, 2015
Last Update Posted Date November 17, 2017
Actual Study Start Date August 4, 2011
Actual Primary Completion Date July 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 29, 2015)
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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 29, 2015)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Clinical Relevance of Microbleeds In Stroke
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
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.

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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood samples
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.

Condition
  • Stroke
  • Atrial Fibrillation (AF)
  • Intracerebral Haemorrhage (ICH)
Intervention Not Provided
Study Groups/Cohorts
  • 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).
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: November 15, 2017)
2490
Original Estimated Enrollment
 (submitted: July 29, 2015)
2500
Actual Study Completion Date October 31, 2017
Actual Primary Completion Date July 31, 2017   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT02513316
Other Study ID Numbers 11/0116
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party University College, London
Study Sponsor University College, London
Collaborators Not Provided
Investigators
Principal Investigator: David Werring UCL
PRS Account University College, London
Verification Date October 2017