Subarachnoid Hemorrhage, AneurysmalMMMSAHNCT03010709
Multimodality Monitoring Directed Management of Aneurysmal Subarachnoid Haemorrhage
An observational study of Subarachnoid Hemorrhage, Aneurysmal, run by Adel Helmy.
Trial summary
Aneurysmal subarachnoid haemorrhage (aSAH) affects up to 10,000 individuals per year in the UK. It accounts for ~5% of strokes, but is responsible for about 25% quality-adjusted life years (QALYs) lost due to stroke. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Feb 2017to Feb 2022
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient with aneurysmal subarachnoid haemorrhage who require intubation and ventilation and admission to the critical care unit.
Who may be able to join
- Aneurysmal Subarachnoid Haemorrhage
- Patient in Neurosciences Critical Care Unit
- Patient likely to survive for at least 24 hours
Who cannot join
- Patient unsuitable for microdialysis monitoring
- bleeding diathesis
- thrombocytopaenia (platelets < 100 x 10e9 per litre)
- Non-survivable brain injury i.e. patient not expected to survive more than 24 hours
Trial locations and contacts
No sites are listed yet.
About this study
Aneurysmal subarachnoid haemorrhage (aSAH) affects up to 10,000 individuals per year in the UK. It accounts for ~5% of strokes, but is responsible for about 25% quality-adjusted life years (QALYs) lost due to stroke. Although early repair of ruptured aneurysms and aggressive postoperative management has improved overall outcomes, it remains a devastating disease with mortality approaching 50%. Survivors are left with neurological injuries that range from subtle cognitive deficit to disabling cerebral infarctions, less than 60% them returning to functional independence.
SAH triggers a series of pathological processes resulting in neuronal damage and consequent neurological deficit termed early brain injury (EBI). Many of the patients who survive the initial bleed, deteriorate days later from delayed ischaemic neurological deficit (DIND), which causes poor outcome or death in up to 30% of patients with SAH. Both of these pathological processes are still poorly understood which limits the number of treatment options.
DIND is treated with blood pressure augmentation to ensure adequate blood flow in the brain. In awake patients, response can be easily and accurately assessed by performing a thorough neurological examination. In patients whose clinical condition demands sedation, intubation and ventilation, assessing response to treatment using the neurological examination is virtually impossible. Multimodality monitoring (MM), primarily microdialysis and brain tissue oxygen tension with catheters inserted into the relevant parts of the brain offer direct assessment of both delivery and utilisation of metabolic substrates at the cellular level. These can be used for early detection of DIND as well as monitoring during blood pressure augmentation. The aim of this study is to establish and validate a clinical protocol for MM derived management of SAH patients, to determine optimal therapies for correcting abnormalities in brain metabolism and explore the relationship between MD and other monitoring modalities.
Read the detailed description
This is a prospective observational study of patients with poor grade subarachnoid haemorrhage (SAH) caused by a ruptured brain artery aneurysm. The investigators aim to include 100 patients over a 5-year period.
SAH is diagnosed using computer tomography imaging of the brain and the presence of a ruptured aneurysm by means of computer tomography angiogram of the vessels of the head. These two investigations are part of the standard clinical practice for every patient with suspected SAH. Term ''poor grade'' is used for cases of SAH where the patient is unconscious i.e. in a coma as a consequence of this disease and whose clinical condition requires intubation and ventilation (with or without sedation) and thus admission to an intensive care unit. All patients with poor grade SAH admitted to the neurosciences critical care unit will be screened for participation in this study. All poor grade SAH patients are unconscious and thus unable to give informed consent. Therefore, the next-of-kin of all eligible patients will be approached to discuss and consider patient's involvement in the study. If there is no next-of-kin, the treating clinician will be approached as a professional consultee.
Once consent is obtained from next-of-kin, the participants will have the following monitoring instituted:
- An intracranial access device will be inserted under general anaesthesia with an intracranial pressure (ICP), a Licox partial tension of tissue oxygen (PbtO2) probe and a microdialysis (MD) catheter. Neuromonitors will be inserted into the part of the brain that is supplied by the affected artery. This procedure will be performed on the neurocritical care unit or in theatre if patients are undergoing other operative procedures at the same time. Continuous neuromonitoring will commence. Hourly MD samples will be processed and the leftover samples stored in -80oC for cytokine analysis at a later date. Neuromonitoring will continue for as long as clinically needed and up to 21 days from ictus.
- All participants will be fitted with a near-infrared spectroscopy monitor (NIRS) . This non-invasive monitor is used to measure tissue haemoglobin concentration and oxygen content continuously and at the bedside.
- Daily transcranial Doppler (TCD) examinations will be performed at the bedside to assess the caliber of large cerebral arteries. This procedure is used in regular clinical practice to diagnose large vessel spasm which is one of the pathological substrates for delayed cerebral ischaemia (DCI) All participants will have a CT brain perfusion scan between day 3 and day 5 from the initial haemorrhage (ictus) or when clinically needed to assess brain perfusion and possibility of DCI which is part of standard clinical practice. These scans are reviewed and reported by consultant neuroradiologists. If they identify an area (or areas) of reversible ischaemia, researchers will review the position of invasive brain monitors - if these are outside of the area of DCI, additional monitors will be inserted into the identified area of reversible ishaemia. Researchers will then use invasive brain monitors (MD and LiCox) and non-invasive monitoring (NIRS and TCD) to assess the response to standard treatment of cerebral reversible ischaemia which is hypertensive therapy i.e. mean arterial pressure (MAP) augmentation with vasoactive medications.
Repeat CT brain perfusion scan will be performed between days 7 and 10 from the initial haemorrhage or earlier if clinically indicated to assess response to treatment.
Following a 6 month period, researchers will see the patients in outpatient clinic to assess functional outcome. This is part of the patient's standard clinical care as all our patients are offered clinical follow up in this way.
Researchers will collect any biological samples that are available as part of the standard clinical care of the participant and will not subject the participants to any additional procedures. This would consist of:
- left over microdialysate samples that are not used for the standard clinical care of the participant
- daily blood samples if the participant has an arterial line or central venous catheter
- samples of cerebrospinal fluid (CSF) if the participant has an external ventricular drain
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Keywords
- Aneurysmal Subarachnoid Haemorrhage, Delayed Ischaemic Neurological Deficit, Induced Hypertension, Partial Brain Tissue Oxygen Tension, Cerebral Microdialysis
- Medical subject headings
- Subarachnoid Hemorrhage
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in brain tissue oxygen tension
Brain Tissue Oxygen measured continuously on Neurointensive Care.
Measured: 10 days
Secondary outcomes (2)
Lactate to pyruvate ratio measured by microdialysis
Microdialysis measured LP ratio measured hourly on Neurointensive Care.
Measured: 10 days
Improved functional outcome of patients as measured by the validated and widely used Extended Glasgow Outcome Scale
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2017 (estimated)
- Study startFeb 2017
- Primary completionFeb 2022 (estimated)
- Study completionFeb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Adel Helmy
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Adel Helmy, University of Cambridge
- Investigators
- Adel Helmy, MBBChir PhD, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03010709
- Sponsor's protocol ID
- A094232
- Acronym
- MMMSAH
- Status last verified
- Jan 2017
- First submitted
- 14 Dec 2016
- Last updated
- 5 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodality Monitoring Directed Management of Aneurysmal Subarachnoid Haemorrhage
- ClinicalTrials.gov ID
- NCT03010709
- Acronym / sponsor ID
- MMMSAH / A094232
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Keywords
- Aneurysmal Subarachnoid Haemorrhage, Delayed Ischaemic Neurological Deficit, Induced Hypertension, Partial Brain Tissue Oxygen Tension, Cerebral Microdialysis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Adel HelmyUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Study start
- Feb 2017
- Primary completion
- Feb 2022 (estimated)
- Study completion
- Feb 2022 (estimated)
- First posted
- 5 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aneurysmal subarachnoid haemorrhage (aSAH) affects up to 10,000 individuals per year in the UK. It accounts for ~5% of strokes, but is responsible for about 25% quality-adjusted life years (QALYs) lost due to stroke. Although early repair of ruptured aneurysms and aggressive postoperative management has improved overall outcomes, it remains a devastating disease with mortality approaching 50%. Survivors are left with neurological injuries that range from subtle cognitive deficit to disabling cerebral infarctions, less than 60% them returning to functional independence.
SAH triggers a series of pathological processes resulting in neuronal damage and consequent neurological deficit termed early brain injury (EBI). Many of the patients who survive the initial bleed, deteriorate days later from delayed ischaemic neurological deficit (DIND), which causes poor outcome or death in up to 30% of patients with SAH. Both of these pathological processes are still poorly understood which limits the number of treatment options.
DIND is treated with blood pressure augmentation to ensure adequate blood flow in the brain. In awake patients, response can be easily and accurately assessed by performing a thorough neurological examination. In patients whose clinical condition demands sedation, intubation and ventilation, assessing response to treatment using the neurological examination is virtually impossible. Multimodality monitoring (MM), primarily microdialysis and brain tissue oxygen tension with catheters inserted into the relevant parts of the brain offer direct assessment of both delivery and utilisation of metabolic substrates at the cellular level. These can be used for early detection of DIND as well as monitoring during blood pressure augmentation. The aim of this study is to establish and validate a clinical protocol for MM derived management of SAH patients, to determine optimal therapies for correcting abnormalities in brain metabolism and explore the relationship between MD and other monitoring modalities.
Detailed description
This is a prospective observational study of patients with poor grade subarachnoid haemorrhage (SAH) caused by a ruptured brain artery aneurysm. The investigators aim to include 100 patients over a 5-year period.
SAH is diagnosed using computer tomography imaging of the brain and the presence of a ruptured aneurysm by means of computer tomography angiogram of the vessels of the head. These two investigations are part of the standard clinical practice for every patient with suspected SAH. Term ''poor grade'' is used for cases of SAH where the patient is unconscious i.e. in a coma as a consequence of this disease and whose clinical condition requires intubation and ventilation (with or without sedation) and thus admission to an intensive care unit. All patients with poor grade SAH admitted to the neurosciences critical care unit will be screened for participation in this study. All poor grade SAH patients are unconscious and thus unable to give informed consent. Therefore, the next-of-kin of all eligible patients will be approached to discuss and consider patient's involvement in the study. If there is no next-of-kin, the treating clinician will be approached as a professional consultee.
Once consent is obtained from next-of-kin, the participants will have the following monitoring instituted:
- An intracranial access device will be inserted under general anaesthesia with an intracranial pressure (ICP), a Licox partial tension of tissue oxygen (PbtO2) probe and a microdialysis (MD) catheter. Neuromonitors will be inserted into the part of the brain that is supplied by the affected artery. This procedure will be performed on the neurocritical care unit or in theatre if patients are undergoing other operative procedures at the same time. Continuous neuromonitoring will commence. Hourly MD samples will be processed and the leftover samples stored in -80oC for cytokine analysis at a later date. Neuromonitoring will continue for as long as clinically needed and up to 21 days from ictus.
- All participants will be fitted with a near-infrared spectroscopy monitor (NIRS) . This non-invasive monitor is used to measure tissue haemoglobin concentration and oxygen content continuously and at the bedside.
- Daily transcranial Doppler (TCD) examinations will be performed at the bedside to assess the caliber of large cerebral arteries. This procedure is used in regular clinical practice to diagnose large vessel spasm which is one of the pathological substrates for delayed cerebral ischaemia (DCI) All participants will have a CT brain perfusion scan between day 3 and day 5 from the initial haemorrhage (ictus) or when clinically needed to assess brain perfusion and possibility of DCI which is part of standard clinical practice. These scans are reviewed and reported by consultant neuroradiologists. If they identify an area (or areas) of reversible ischaemia, researchers will review the position of invasive brain monitors - if these are outside of the area of DCI, additional monitors will be inserted into the identified area of reversible ishaemia. Researchers will then use invasive brain monitors (MD and LiCox) and non-invasive monitoring (NIRS and TCD) to assess the response to standard treatment of cerebral reversible ischaemia which is hypertensive therapy i.e. mean arterial pressure (MAP) augmentation with vasoactive medications.
Repeat CT brain perfusion scan will be performed between days 7 and 10 from the initial haemorrhage or earlier if clinically indicated to assess response to treatment.
Following a 6 month period, researchers will see the patients in outpatient clinic to assess functional outcome. This is part of the patient's standard clinical care as all our patients are offered clinical follow up in this way.
Researchers will collect any biological samples that are available as part of the standard clinical care of the participant and will not subject the participants to any additional procedures. This would consist of:
- left over microdialysate samples that are not used for the standard clinical care of the participant
- daily blood samples if the participant has an arterial line or central venous catheter
- samples of cerebrospinal fluid (CSF) if the participant has an external ventricular drain
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient with aneurysmal subarachnoid haemorrhage who require intubation and ventilation and admission to the critical care unit.
Key inclusion criteria (3 listed)
- Aneurysmal Subarachnoid Haemorrhage
- Patient in Neurosciences Critical Care Unit
- Patient likely to survive for at least 24 hours
Key exclusion criteria (4 listed)
- Patient unsuitable for microdialysis monitoring
- Non-survivable brain injury i.e. patient not expected to survive more than 24 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Improvement in brain tissue oxygen tension
Time frame: 10 days
Brain Tissue Oxygen measured continuously on Neurointensive Care.
2 secondary outcomes
Lactate to pyruvate ratio measured by microdialysis
Time frame: 10 days
Improved functional outcome of patients as measured by the validated and widely used Extended Glasgow Outcome Scale
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adel Helmy, MBBChir PhD principal investigator
Cambridge University Hospitals NHS Foundation Trust
Questions about this trial
What is this clinical trial studying?
An observational study of Subarachnoid Hemorrhage, Aneurysmal, run by Adel Helmy.
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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 5 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adel Helmy, MBBChir PhD (07855064515, adelhelmy@doctors.org.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in brain tissue oxygen tension (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jan 2017.