Study protocol for SFX-01 after subarachnoid haemorrhage (SAS): a multicentre randomised double-blinded, placebo controlled trial

IntroductionSubarachnoid haemorrhage (SAH) from a ruptured cerebral aneurysm carries high morbidity and mortality. Despite huge advances in techniques to secure the aneurysm, there has been little progress in the treatment of the deleterious effects of the haemorrhage.Sulforaphane is an Nrf2 inducer with anti-oxidant and anti-inflammatory properties. It has been shown to improve clinical outcome in experimental models of SAH, but is unstable. SFX-01 (Evgen Pharma) is a novel composition comprised of synthetic sulforaphane stabilised within an α-cyclodextrin complex. On ingestion, the complex releases sulforaphane making SFX-01 an ideal vehicle for delivery of sulforaphane.Methods and analysisThe objective of the study is to assess the safety, pharmacokinetics and efficacy of SFX-01. This is a prospective, multicentre, randomised, double-blind placebo-controlled trial in patients aged 18–80 years with aneurysmal subarachnoid haemorrhage in the previous 48 hours. 90 patients will be randomised to receive SFX-01 (300 mg) or placebo two times per day for up to 28 days.Safety will be assessed using blood tests and adverse event reporting.Pharmacokinetics will be assessed based on paired blood and cerebrospinal fluid (CSF) sulforaphane levels on day 7. A subgroup will have hourly samples taken during 6 hours post-dosing on days 1 and 7. Pharmacodynamics will be assessed by haptoglobin and malondialdehyde levels, and maximum flow velocity of middle cerebral artery will be measured by transcranial Doppler ultrasound.Clinical outcomes will be assessed at days 28, 90 and 180 with modified Rankin Scale, Glasgow Outcome Score, SAH Outcome Tool, Short Form-36, Brain Injury Community Rehabilitation Outcome Scales and Check List for Cognitive and Emotional consequences following stroke. MRI at 6 months including quantitative susceptibility mapping and volumetric T1 will measure iron deposition and cortical volume.Safety, CSF sulforaphane concentration and middle cerebral artery flow velocity will be primary outcomes and all others secondary.Ethics and disseminationEthical approval was obtained from South Central Hampshire A committee. Outcomes of the trial will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT02614742.

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Correlation of the middle cerebral artery flow velocity with the clinical course and CT-visualized subarachnoid blood in patients after aneurysmal subarachnoid haemorrhage

Timing of Aneurysm Surgery ◽

10.1515/9783110858853-056 ◽

1985 ◽

pp. 429-436

Keyword(s):

Subarachnoid Haemorrhage ◽

Middle Cerebral Artery ◽

Flow Velocity ◽

Cerebral Artery ◽

Clinical Course ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Subarachnoid Blood ◽

Artery Flow

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Placing intracerebral probes to optimise detection of delayed cerebral ischemia and allow for the prediction of patient outcome in aneurysmal subarachnoid haemorrhage

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16675880 ◽

2016 ◽

Vol 37 (8) ◽

pp. 2820-2832 ◽

Cited By ~ 6

Author(s):

Yannick Tholance ◽

Gleicy K Barcelos ◽

Armand Perret-Liaudet ◽

Edris Omar ◽

Romain Carrillon ◽

...

Keyword(s):

Patient Outcome ◽

Cerebral Ischemia ◽

Subarachnoid Haemorrhage ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Delayed Cerebral Ischemia ◽

Detection Sensitivity ◽

Cerebral Microdialysis ◽

Anterior Communicating Artery ◽

Aneurysmal Subarachnoid Haemorrhage

Cerebral microdialysis could be useful to detect delayed cerebral ischemia in aneurysmal subarachnoid haemorrhage patients. The optimal location of the probes, however, remains controversial. Here, we determined the vascular territories with the highest infarct risk in relation to aneurysm location to define probe implantation guidelines. These guidelines were retrospectively validated by studying the likelihood of probe to fall in a secondary infarct area, and by analysing their influence to predict patient outcome. The vascular territories with highest risk of infarction were the anterior cerebral arteries for anterior communicating artery aneurysms and the ipsilateral middle cerebral artery for internal carotid artery, posterior communicating artery and middle cerebral artery aneurysms. When cerebral microdialysis probes had been implanted in these territories, 79% were located within an infarcted area versus 54% when they were implanted in other territories. Delayed cerebral ischemia was detected only when the probe was located within a brain area later affected by secondary infarction, which could justify the use of implantation guidelines. Moreover, individual patient outcomes could be predicted when probes were placed in the brain territories as suggested by this study. Thus, a precise probe placement algorithm can improve delayed cerebral ischemia detection sensitivity and allow for a better prediction concerning patient outcome.

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SIGNIFICANTLY LOWER RIGHT MIDDLE CEREBRAL ARTERY BLOOD FLOW VELOCITY IN THE FIRST EPISODE OF PSYCHOSIS DURING NEUROCOGNITIVE TESTING

Psychiatria Danubina ◽

10.24869/spsih.2018.172 ◽

2018 ◽

Vol 30 (2) ◽

pp. 172-182 ◽

Cited By ~ 1

Author(s):

Ivana Kekin ◽

◽

Dina Bosnjak ◽

Porin Makaric ◽

Zarko Bajic ◽

...

Keyword(s):

Blood Flow ◽

Middle Cerebral Artery ◽

Flow Velocity ◽

Cerebral Artery ◽

Blood Flow Velocity ◽

First Episode ◽

Artery Blood Flow ◽

Neurocognitive Testing

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Faculty Opinions recommendation of Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13198963.14726480 ◽

2011 ◽

Author(s):

Luciana Mascia ◽

Ilaria Mastromauro

Keyword(s):

Subarachnoid Haemorrhage ◽

Receptor Antagonist ◽

Endothelin Receptor Antagonist ◽

Aneurysmal Subarachnoid Haemorrhage ◽

Endothelin Receptor ◽

Surgical Clipping ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo

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Faculty Opinions recommendation of Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.719895089.793510612 ◽

2015 ◽

Author(s):

Peter Andrews

Keyword(s):

Subarachnoid Haemorrhage ◽

Controlled Trial ◽

Aneurysmal Subarachnoid Haemorrhage

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The role of sildenafil citrate in the treatment of fetal growth restriction: a randomized controlled trial

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20191929 ◽

2019 ◽

Vol 8 (5) ◽

pp. 1840

Author(s):

Ahmed Abdelshafy ◽

Khaled Ibrahim Abdullah ◽

Sherif Ashoush ◽

Heba E. Hosni

Keyword(s):

Middle Cerebral Artery ◽

Fetal Growth ◽

Cerebral Artery ◽

Fetal Growth Restriction ◽

Umbilical Artery ◽

Controlled Trial ◽

Maternity Hospital ◽

Growth Restriction ◽

Sildenafil Citrate ◽

Doppler Velocity

Background: This study was aimed to evaluate the effect of sildenafil citrate on Doppler velocity indices in patients with fetal growth restriction (FGR) associated with impaired placental circulation.Methods: A double-blinded, parallel group randomized clinical trial (clinicaltrials.gov NCT02590536) was conducted in Ain Shams Maternity Hospital, in the period between October 2015 and June 2017. Ninety pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were randomized to either sildenafil citrate 25 mg orally every 8 hours or placebo visually-identical placebo tablets with the same regimen. The primary outcome of the study was the change in umbilical artery and fetal middle cerebral artery indices.Results: There was a significant improvement in umbilical and middle cerebral artery indices after sildenafil administration p<0.001. Present study observed that, sildenafil group, in comparison to placebo, has a significantly higher mean neonatal birth weight. 1783±241g vs 1570±455g (p<0.001). There was a significantly higher mean gestational age at delivery in women in sildenafil group 35.3±1.67 weeks, whereas it was lower in the placebo group 33.5±1.7 weeks. The side effects as headache, palpitation and facial flushing were significantly higher in sildenafil group compared to placebo group.Conclusions: The use sildenafil citrate in pregnancies with fetal growth restriction (FGR) improved the feto-placental Doppler indices (pulsatility index of umbilical artery and middle cerebral artery) and improved neonatal outcomes.

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Aneurysm Arising at the Origin of a Duplicated Middle Cerebral Artery

Case Reports in Neurology ◽

10.1159/000517366 ◽

2021 ◽

pp. 446-450

Author(s):

Jean Roch Alliez ◽

Luis Manera

Keyword(s):

Computed Tomography ◽

Subarachnoid Haemorrhage ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

World Federation ◽

Treatment Procedure ◽

3D Computed Tomography ◽

Ruptured Aneurysms ◽

Tomography Reconstruction ◽

Computed Tomography Reconstruction

A duplicated middle cerebral artery (DMCA) is a common anomaly. However, aneurysms arising from the origin of a DMCA are extremely rare. A 22-year-old female was admitted to our hospital with a World Federation of Neurosurgical Societies grade 2 subarachnoid haemorrhage. Four-vessel angiography revealed a DMCA and an aneurysm arising from the origin of this artery. The aneurysm was successfully treated by embolization, and the patient was discharged 2 weeks later. Ruptured aneurysms arising from the origin of a DMCA can be successfully treated by embolization. These aneurysms are small and 3D-computed tomography reconstruction is mandatory to detect them. It is important to preserve the DMCA during the treatment procedure.

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