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StrokeCROMIS-2NCT02513316

Clinical Relevance of Microbleeds In Stroke

An observational study of Stroke and Atrial Fibrillation (AF), run by University College, London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Type of treatment
Pill or oral medicine
How many people
2,490 participants
Where
1 siteUnited Kingdom
Study dates
4 Aug 2011to 31 Oct 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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
  • 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

Who cannot join

  • 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)
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • UCL

    London, WC1N 3BG

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Keywords
Microbleeds
Medical subject headings
Stroke, Atrial Fibrillation, Cerebral Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02513316
Study groupRoleWhat they receive
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 being measured

The primary outcome is the main question the study is designed to answer.

  1. Symptomatic intracranial haemorrhage

    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.

    Measured: 24 months

Secondary outcomes (5)
  1. Ischaemic stroke

    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.

    Measured: 24 months

  2. Transient Ischaemic Attack (TIA)

    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.

    Measured: 24 months

  3. Death

    Patient death (of any cause). Assessed by General Practitioner (GP) follow up, recruiting hospital records and National Health Service (NHS) Information Centre data systems.

    Measured: 24 months

  4. Any other major haemorrhagic events other than ICH

    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.

    Measured: 24 months

  5. Long term physical disability

    Assessed by administering Modified Rankin Score (mRS) to patients at 6,12 and 24 months via patient questionnaire.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2015 (estimated)
  2. Study start4 Aug 2011
  3. Primary completion31 Jul 2017
  4. Study completion31 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
2,490 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02513316
Sponsor's protocol ID
11/0116
Acronym
CROMIS-2
Status last verified
Oct 2017
First submitted
29 Jul 2015
Last updated
17 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Seiffge DJ, Wilson D, Ambler G, Banerjee G, Hostettler IC, Houlden H, Shakeshaft C, Cohen H, Yousry TA, Al-Shahi Salman R, Lip G, Brown MM, Muir K, Jager HR, Werring DJ. Small vessel disease burden and intracerebral haemorrhage in patients taking oral anticoagulants. J Neurol Neurosurg Psychiatry. 2021 Mar 19;92(8):805-14. doi: 10.1136/jnnp-2020-325299. Online ahead of print.

    PubMed 33741739
  • Hostettler IC, Schwarz G, Ambler G, Wilson D, Banerjee G, Seiffge DJ, Shakeshaft C, Lunawat S, Cohen H, Yousry TA, Al-Shahi Salman R, Lip GYH, Brown MM, Muir KW, Houlden H, Jager HR, Werring DJ; CROMIS-2 Collaborators. Cerebral Small Vessel Disease and Functional Outcome Prediction After Intracerebral Hemorrhage. Neurology. 2021 Apr 13;96(15):e1954-e1965. doi: 10.1212/WNL.0000000000011746. Epub 2021 Feb 24.

    PubMed 33627495
  • Du H, Wilson D, Ambler G, Banerjee G, Shakeshaft C, Cohen H, Yousry T, Al-Shahi Salman R, Lip GYH, Houlden H, Brown MM, Muir KW, Jager HR, Werring DJ; Clinical Relevance of Microbleeds in Stroke (CROMIS-2) Collaborators. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia. Stroke. 2021 Jan;52(1):91-99. doi: 10.1161/STROKEAHA.120.029474. Epub 2020 Dec 7.

    PubMed 33280548
  • Banerjee G, Wilson D, Ambler G, Hostettler IC, Shakeshaft C, Cohen H, Yousry T, Al-Shahi Salman R, Lip GYH, Houlden H, Muir KW, Brown MM, Jager HR, Werring DJ; CROMIS-2 collaborators. Longer term stroke risk in intracerebral haemorrhage survivors. J Neurol Neurosurg Psychiatry. 2020 Aug;91(8):840-845. doi: 10.1136/jnnp-2020-323079. Epub 2020 Jun 17.

    PubMed 32554800
  • Banerjee G, Chan E, Ambler G, Wilson D, Cipolotti L, Shakeshaft C, Cohen H, Yousry T, Al-Shahi Salman R, Lip GYH, Muir KW, Brown MM, Jager HR, Werring DJ; CROMIS-2 Collaborators dagger; CROMIS-2 Collaborators<xref ref-type="author-note" rid="jah34726-note-1002"><sup>dagger</sup></xref>. Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events: Neuroimaging and Prognostic Associations. J Am Heart Assoc. 2020 Jan 7;9(1):e014537. doi: 10.1161/JAHA.119.014537. Epub 2020 Jan 4.

    PubMed 31902325
  • Wilson D, Ambler G, Shakeshaft C, Banerjee G, Charidimou A, Seiffge D, White M, Cohen H, Yousry T, Salman R AS, Lip GYH, Muir K, Brown MM, Jager HR, Werring DJ; CROMIS-2 collaborators. Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA. BMJ Open. 2019 Jul 24;9(7):e028387. doi: 10.1136/bmjopen-2018-028387.

    PubMed 31345970
  • Wilson D, Ambler G, Banerjee G, Shakeshaft C, Cohen H, Yousry TA, Al-Shahi Salman R, Lip GYH, Houlden H, Brown MM, Muir KW, Jager HR, Werring DJ; Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators. Early versus late anticoagulation for ischaemic stroke associated with atrial fibrillation: multicentre cohort study. J Neurol Neurosurg Psychiatry. 2019 Mar;90(3):320-325. doi: 10.1136/jnnp-2018-318890. Epub 2018 Nov 19.

    PubMed 30455404
  • Wilson D, Ambler G, Shakeshaft C, Brown MM, Charidimou A, Al-Shahi Salman R, Lip GYH, Cohen H, Banerjee G, Houlden H, White MJ, Yousry TA, Harkness K, Flossmann E, Smyth N, Shaw LJ, Warburton E, Muir KW, Jager HR, Werring DJ; CROMIS-2 collaborators. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol. 2018 Jun;17(6):539-547. doi: 10.1016/S1474-4422(18)30145-5. Epub 2018 May 16.

    PubMed 29778365
  • Banerjee G, Wilson D, Ambler G, Osei-Bonsu Appiah K, Shakeshaft C, Lunawat S, Cohen H, Yousry T Dr, Lip GYH, Muir KW, Brown MM, Al-Shahi Salman R, Jager HR, Werring DJ; CROMIS-2 Collaborators. Cognitive Impairment Before Intracerebral Hemorrhage Is Associated With Cerebral Amyloid Angiopathy. Stroke. 2018 Jan;49(1):40-45. doi: 10.1161/STROKEAHA.117.019409. Epub 2017 Dec 15.

    PubMed 29247143
  • Charidimou A, Wilson D, Shakeshaft C, Ambler G, White M, Cohen H, Yousry T, Al-Shahi Salman R, Lip G, Houlden H, Jager HR, Brown MM, Werring DJ. The Clinical Relevance of Microbleeds in Stroke study (CROMIS-2): rationale, design, and methods. Int J Stroke. 2015 Oct;10 Suppl A100:155-61. doi: 10.1111/ijs.12569. Epub 2015 Aug 2.

    PubMed 26235450

Questions about this trial

What is this clinical trial studying?

An observational study of Stroke and Atrial Fibrillation (AF), run by University College, London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Symptomatic intracranial haemorrhage (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02513316, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2017.

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