Philip M. Bath (United Kingdom)
University of Nottingham Stroke, Mental Health & Clinical NeuroscienceAuthor Of 5 Presentations
WSO President’s Award
ONGOING CLINICAL TRIAL: A PROSPECTIVE MULTICENTRE, PHASE 2B RANDOMISED, CONTROLLED DOUBLE-BLIND TRIAL TO DETERMINE THE SAFETY AND EFFICACY OF PERISPINAL ETANERCEPT ON QUALITY OF LIFE
Abstract
Background and Aims
There are few treatment options for stroke survivors with ongoing impairments. Recently, the beneficial effects of a tumor necrosis factor inhibitor, etanercept, has caught the attention of the media and the stroke survivor community. Observational, uncontrolled studies suggest substantial improvements of chronic impairments after a single administration of etanercept, injected subcutaneously in the perispinal region. Large, randomized controlled trials have not been conducted.
Methods
The Perispinal Etanercept for STroke Outcomes trial (ACTRN12620001011976) is a 30-months, phase 2b, multicenter, randomized, double blind, placebo-controlled trial testing the safety and efficacy of administration of perispinal etanercept in improving patient reported outcomes at 28 days after treatment. The required sample size is 168. Eligible patients are aged ≤65 years at time of stroke, between 1-5 year after the index stroke, with a current modified Rankin scale of 3 to 5. The primary efficacy hypothesis is that treatment with perispinal etanercept improves quality of life in stroke survivors, as measured with the Short Form-36. The secondary hypothesis is that repeated injection of etanercept leads to improved quality of life compared to a single injection. Other exploratory outcome measures include the NIHSS, MOCA, FIM, modified Rankin scale, pain VAS, FAS, PHQ-9, GAD-7.
Results
The trial is ongoing with 36 patients enrolled as of May 14 2021 at sites in Australia and New Zealand.
Conclusions
The promise of etanercept to improve quality of life in chronic stroke survivors needs to be tested. PESTO will inform the stroke community about the efficacy and safety of this intervention.
EFFECTS OF RATIO OF HAEMATOMA VOLUME TO INTRACRANIAL VOLUME ON HAEMATOMA GROWTH AND MASS EFFECT: POST-HOC ANALYSIS OF RIGHT-2 TRIAL
Abstract
Background and Aims
The risk of haematoma expansion in intracerebral haemorrhage (ICH) increases with larger baseline volume until haemostasis or a tamponade is effected by the rigid cranium. We explored the association of ICH volume to intracranial volume ratio (ICH/ICV) with mass effect and whether it could predict haematoma expansion at 24-hour.
Methods
CT scans of 133 patients with ICH in the RIGHT-2 trial were analysed. ICH/ICV ratio (%) was estimated using semi-automated segmentation methods. Significant mass effect was defined as midline shift of ≥5mm or ambient cistern score of ≥1 (effacement of at least one ambient cistern). Multivariable logistic regression with adjustment for baseline variables was performed to explore the predictors of haematoma expansion (>6mL or >33%) and significant mass effect.
Results
The mean baseline ICH volume was 37.8 (38.6) mL and mean ICH/ICV ratio 2.68 (2.72)%. ICH/ICV ratio of ≥6% was significantly associated with ambient cistern effacement (adjusted odd ratio [aOR] 21.6, 95%CI 5.5-84.8) and midline shift ≥5mm (aOR 220) on baseline CT but not at lower cut-offs. Increasing ICH/ICV ratio predicted haematoma expansion but the effect plateaued at 3-4% when further increase did not significantly increase the aOR (Figure 1). The accuracy of ICH/ICV ratio in predicting haematoma expansion was similar compared to ICH volume (area under the receiver operator characteristics curve 0.69 for both, Figure 2).
Conclusions
ICH/ICV ratio predicted haematoma expansion and may be used to prognosticate or stratify patients in stroke trials testing potential treatments. The potential mechanisms and effect on functional outcomes need further exploration.
POLIPILL AND RISCOMETER TO PREVENT STROKE AND COGNITIVE IMPAIRMENT IN PRIMARY HEALTH CARE - PROMOTE STUDY
Abstract
Background and Aims
The increase burden of stroke and dementia provides strong evidence that currently used primary prevention strategies are not enough and 80% of strokes occur in people with low to moderate risk. The purpose is to test whether a polypill used alone or in combination with lifestyle modification will reduce the incidence of stroke and cognitive impairment in a population of individuals with low to moderate risk of stroke.
Methods
Phase III Randomized Clinical Trial, prospective, factorial 2x2, of 12,268 subjects followed by 3 years. 60 Health Units will be randomized (clusters) to use or not the approach of community health workers with the Stroke Riskometer. After a run-in phase (30 days, all participants with active drug), patients will be randomized to receive the polypill (valsartan 80 mg, anlodipina 5 mg e rosuvastatina 10 mg) or placebo (dose adjustment of amlodipine 2,5 for patients with adverse events). It will be included: (1)adults aged 50-75 years; (2) no previous history of stroke, TIA or cardiovascular disease; (3)systolic blood pressure (BP) 120-139 mmHg; (4) one or more lifestyle risk factors (smoking, overweight, physical inactivity or inadequate diet. It will be excluded patients with hypercholesterolemia or diabetes or take other antihypertensive drugs or open label statins. Subjects will be randomized under a minimization process using age, sex, BP, education level, total cholesterol.
Results
We expect to reduce in 50% the risk of stroke and cognitive decline in 3 years.
Conclusions
With the trial results we expect to change the public prevention policies in primary care.
XANTHINE OXIDASE INHIBITION FOR IMPROVEMENT OF LONG-TERM OUTCOMES FOLLOWING ISCHAEMIC STROKE AND TRANSIENT ISCHAEMIC ATTACK (XILO-FIST)
Abstract
Background and Aims
People who suffer an ischaemic stroke are at risk of recurrent vascular events. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity progression (WMH) and systolic blood pressure (SBP) following ischaemic stroke.
Methods
In this multicenter, prospective, randomised, blinded, controlled trial we assigned participants within 30-days of ischaemic stroke or TIA to receive allopurinol 300mg twice daily or placebo for 104 weeks (registration number NCT02122718). All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS). Secondary outcomes included change in day-time SBP. Analyses were by intention to treat.
Results
We randomised 464 participants (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS was 1.33 (SD 1.79) with allopurinol and 1.51 (SD 1.89) with placebo, between group difference -0.17, 95% CI -0.52 to 0.17, p=0.33. The change in day-time SBP at week 4 was -2.3 mmHg (SD 12.92) with allopurinol and 0.8 (SD 10.74) with placebo, between group difference -3.33, 95% CI -5.55 to -1.11, p=0.0034. At week 104, the between group difference in day-time SBP was -2.95 mmHg, 95% CI -6.00 to 0.10, p=0.058.
Conclusions
Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA but did lower SBP. Further research should explore whether this blood pressure change is clinically important.
Presenter of 1 Presentation
WSO President’s Award
Moderator of 1 Session
