Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2)
Cerebral small vessel disease (cSVD) causes lacunar stroke (25% of ischaemic strokes), haemorrhage, dementia, physical frailty, or is ‘covert’, but has no specific treatment. Uncertainties about the design of clinical trials in cSVD, which patients to include or outcomes to assess, may have delayed...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
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| Series: | Stroke and Vascular Neurology |
| Online Access: | https://svn.bmj.com/content/early/2024/04/03/svn-2023-003022.full |
| _version_ | 1797224751088795648 |
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| author | Joanna M Wardlaw Philip M Bath Jason P Appleton Lisa J Woodhouse Iris Mhlanga Fergus Doubal Gordon Blair |
| author_facet | Joanna M Wardlaw Philip M Bath Jason P Appleton Lisa J Woodhouse Iris Mhlanga Fergus Doubal Gordon Blair |
| author_sort | Joanna M Wardlaw |
| collection | DOAJ |
| description | Cerebral small vessel disease (cSVD) causes lacunar stroke (25% of ischaemic strokes), haemorrhage, dementia, physical frailty, or is ‘covert’, but has no specific treatment. Uncertainties about the design of clinical trials in cSVD, which patients to include or outcomes to assess, may have delayed progress. Based on experience in recent cSVD trials, we reviewed ways to facilitate future trials in patients with cSVD.We assessed the literature and the LACunar Intervention Trial 2 (LACI-2) for data to inform choice of Participant, Intervention, Comparator, Outcome, including clinical versus intermediary endpoints, potential interventions, effect of outcome on missing data, methods to aid retention and reduce data loss. We modelled risk of missing outcomes by baseline prognostic variables in LACI-2 using binary logistic regression.Imaging versus clinical outcomes led to larger proportions of missing data. We present reasons for and against broad versus narrow entry criteria. We identified numerous repurposable drugs with relevant modes of action to test in various cSVD subtypes. Cognitive impairment is the most common clinical outcome after lacunar ischaemic stroke but was missing more frequently than dependency, quality of life or vascular events in LACI-2. Assessing cognitive status using Diagnostic and Statistical Manual for Mental Disorders Fifth Edition can use cognitive data from multiple sources and may help reduce data losses.Trials in patients with all cSVD subtypes are urgently needed and should use broad entry criteria and clinical outcomes and focus on ways to maximise collection of cognitive outcomes to avoid missing data. |
| first_indexed | 2024-04-24T13:58:05Z |
| format | Article |
| id | doaj.art-a3b2145f031f4c77a8f7a1b291dde798 |
| institution | Directory Open Access Journal |
| issn | 2059-8696 |
| language | English |
| last_indexed | 2024-04-24T13:58:05Z |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Stroke and Vascular Neurology |
| spelling | doaj.art-a3b2145f031f4c77a8f7a1b291dde7982024-04-03T17:20:09ZengBMJ Publishing GroupStroke and Vascular Neurology2059-869610.1136/svn-2023-003022Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2)Joanna M Wardlaw0Philip M Bath1Jason P Appleton2Lisa J Woodhouse3Iris Mhlanga4Fergus Doubal5Gordon Blair6Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UKStroke Trials Unit, Mental Health & Clinical Neuroscience, University of Nottingham, Nottingham, UKStroke Trials Unit, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham, UKStroke Trials Unit, Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, UKStroke Trials Unit, University of Nottingham, Nottingham, UKCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UKUniversity of Edinburgh, Edinburgh, UKCerebral small vessel disease (cSVD) causes lacunar stroke (25% of ischaemic strokes), haemorrhage, dementia, physical frailty, or is ‘covert’, but has no specific treatment. Uncertainties about the design of clinical trials in cSVD, which patients to include or outcomes to assess, may have delayed progress. Based on experience in recent cSVD trials, we reviewed ways to facilitate future trials in patients with cSVD.We assessed the literature and the LACunar Intervention Trial 2 (LACI-2) for data to inform choice of Participant, Intervention, Comparator, Outcome, including clinical versus intermediary endpoints, potential interventions, effect of outcome on missing data, methods to aid retention and reduce data loss. We modelled risk of missing outcomes by baseline prognostic variables in LACI-2 using binary logistic regression.Imaging versus clinical outcomes led to larger proportions of missing data. We present reasons for and against broad versus narrow entry criteria. We identified numerous repurposable drugs with relevant modes of action to test in various cSVD subtypes. Cognitive impairment is the most common clinical outcome after lacunar ischaemic stroke but was missing more frequently than dependency, quality of life or vascular events in LACI-2. Assessing cognitive status using Diagnostic and Statistical Manual for Mental Disorders Fifth Edition can use cognitive data from multiple sources and may help reduce data losses.Trials in patients with all cSVD subtypes are urgently needed and should use broad entry criteria and clinical outcomes and focus on ways to maximise collection of cognitive outcomes to avoid missing data.https://svn.bmj.com/content/early/2024/04/03/svn-2023-003022.full |
| spellingShingle | Joanna M Wardlaw Philip M Bath Jason P Appleton Lisa J Woodhouse Iris Mhlanga Fergus Doubal Gordon Blair Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2) Stroke and Vascular Neurology |
| title | Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2) |
| title_full | Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2) |
| title_fullStr | Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2) |
| title_full_unstemmed | Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2) |
| title_short | Design of trials in lacunar stroke and cerebral small vessel disease: review and experience with the LACunar Intervention Trial 2 (LACI-2) |
| title_sort | design of trials in lacunar stroke and cerebral small vessel disease review and experience with the lacunar intervention trial 2 laci 2 |
| url | https://svn.bmj.com/content/early/2024/04/03/svn-2023-003022.full |
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