Clinical Relevance of Microbleeds In Stroke (CROMIS-2)

November 15, 2017 updated by: University College, London

Microbleeds and Genetic Risk Factors to Predict the Risk of Intracranial Haemorrhage in Patients Treated With Anticoagulation Following Cardioembolic Stroke Due to Atrial Fibrillation

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.

Study Overview

Status

Completed

Conditions

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

Enrollment (Actual)

2490

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 months
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.
24 months
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.
24 months
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.
24 months
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.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Investigators

  • Principal Investigator: David Werring, UCL

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 4, 2011

Primary Completion (Actual)

July 31, 2017

Study Completion (Actual)

October 31, 2017

Study Registration Dates

First Submitted

July 29, 2015

First Submitted That Met QC Criteria

July 29, 2015

First Posted (Estimate)

July 31, 2015

Study Record Updates

Last Update Posted (Actual)

November 17, 2017

Last Update Submitted That Met QC Criteria

November 15, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11/0116

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stroke

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in France

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe