Clinical Relevance of Microbleeds In Stroke

NCT02513316 | Completed

• 1 other identifier: 11/0116
• Study Type: observational
• Target: 2,490
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke; Atrial Fibrillation (AF); Intracerebral Haemorrhage (ICH)

Keywords

Microbleeds

Outcome Measures

Primary Outcomes (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.

  24 months

Secondary Outcomes (5)

• Ischaemic stroke

  24 months

• Transient Ischaemic Attack (TIA)

  24 months

• Death

  24 months

• Any other major haemorrhagic events other than ICH

  24 months

• Long term physical disability

  24 months

Study Arms (2)

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).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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
• 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

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

UCL

London, WC1N 3BG, United Kingdom

Location

Related Publications (10)

• 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.

  PMID: 33741739 DERIVED

• 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.

  PMID: 33627495 DERIVED

• 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.

  PMID: 33280548 DERIVED

• 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.

  PMID: 32554800 DERIVED

• 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">^dagger</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.

  PMID: 31902325 DERIVED

• 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.

  PMID: 31345970 DERIVED

• 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.

  PMID: 30455404 DERIVED

• 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.

  PMID: 29778365 DERIVED

• 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.

  PMID: 29247143 DERIVED

• 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.

  PMID: 26235450 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Stroke; Atrial Fibrillation; Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Hemorrhages; Hemorrhage

Study Officials

• David Werring

  UCL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2015
• First Posted: July 31, 2015
• Study Start: August 4, 2011
• Primary Completion: July 31, 2017
• Study Completion: October 31, 2017
• Last Updated: November 17, 2017

Record last verified: 2017-10

Locations

GB (1)