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Trial registered on ANZCTR


Registration number
ACTRN12623000970640
Ethics application status
Approved
Date submitted
18/04/2023
Date registered
6/09/2023
Date last updated
25/08/2024
Date data sharing statement initially provided
6/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The efficacy of lumbar puncture in reducing intracranial pressure after stroke
Scientific title
A safety and feasibility study of the capacity of lumbar puncture to reduce elevated intracranial pressure in acute ischaemic stroke.
Secondary ID [1] 308175 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 327898 0
Elevated intracranial pressure 327899 0
Condition category
Condition code
Stroke 324987 324987 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial aims to determine whether aspiration of cerebrospinal fluid via lumbar puncture is a safe and feasible treatment to maintain intracranial pressure at 4-8 cm H2O after stroke.

All procedures will take place after standard acute stroke care has been administered and within 24 hours of the stroke occurrence. All procedures will be undertaken by a clinician. Patients will undergo non-invasive intracranial pressure (nICP) monitoring using transcranial Doppler ultrasound and non-invasive peripheral arterial waveform monitoring. Time of lumbar puncture will be recorded. Close neurological observation will be conducted primarily during the first 48 hours after treatment administration according to local clinical practice. Lumbar puncture will take 30-45 minutes to complete. Undertaking of lumbar puncture will be noted by clinician in the patient medical records.

Lumbar puncture involves insertion of a needle into the spinal canal to collect cerebrospinal fluid (CSF). The procedure is performed under local anaesthesia with a hypodermic needle. The person is placed on their side and bends their neck, so the chin is close to the chest, hunches their back, and brings their knees toward their chest (similar to a foetal position). The lower back is prepared using aseptic technique and local anaesthetic applied. A spinal needle is inserted between the lumbar vertebrae L3/L4, L4/L5, or L5/S1 and pushed until there is a ‘give’ as it enters the lumbar cistern. The needle is pushed further until there is a second ‘give’ that indicates the needle is now past the dura mater. The stylet from the spinal needle is then withdrawn and CSF is collected. The procedure is ended by withdrawing the needle while placing pressure on the puncture site.

Non-invasive monitoring of intracranial pressure (nICP) involves use of two routinely clinically used non-invasive, painless procedures; transcranial Doppler ultrasound and non-invasive peripheral arterial waveform monitoring. Blood flow and pressure in the peripheral circulation and the brain are measured and the difference between the two is used to estimate the ICP. Transcranial Doppler ultrasound involves participants being fitted with a semi-rigid headpiece that uses sound waves to examine blood flow in the brain. Peripheral arterial waveform monitoring is done via finger cuff plethysmography which uses light to measure blood flow.
Intervention code [1] 324624 0
Treatment: Other
Comparator / control treatment
Comparator group are historical and will have received standard acute stroke care. They will not be exposed to lumbar puncture. Historical data will be collected from participants fitting eligibility criteria who were admitted to the John Hunter Hospital for a stroke from 2nd December 2015 - 6th September 2023.
Standard stroke care involves baseline multimodal CT or MRI, blood sample collection, assessment for acute stroke therapy (thromboylsis and/or endovascular clot retrieval), follow-up MRI or non-contrast CT head scan and computed tomographic angiogram (CTA) at 24-48 hours.
Control group
Historical

Outcomes
Primary outcome [1] 332807 0
Absence of lumbar puncture complications (i.e., bleeding, low-pressure headache). A study-specific questionnaire will be used to determine whether the lumabr puncture prodecure was acceptable in terms of discomfort to the patient. Acceptability score of equal to or less than 30 out of a possible total of 40 points (75%) is required to deem the procedure ‘feasible’.
Timepoint [1] 332807 0
Up to 3 months after stroke.
Secondary outcome [1] 414740 0
Safety (to be assessed as a composite outcome): Any patients with neurological deterioration, death due to any cause, or modified Rankin Score (mRS) of 5-6 (severe disability or death). Neurological deterioration will be assessed using the National Institutes of Health Stroke Score (NIHSS).
Timepoint [1] 414740 0
3 months after stroke
Secondary outcome [2] 414741 0
Feasibility: Ability to recruit within planned timeframe as assessed by recruitment logs.
Timepoint [2] 414741 0
Upon conclusion of the study.
Secondary outcome [3] 414742 0
Feasibility: perform lumbar puncture within 24 hours of last time seen well as determined by assessing patient medical records.
Timepoint [3] 414742 0
24 hours after commencement of stroke symptoms.
Secondary outcome [4] 414743 0
Feasibility: Patient feedback regarding procedure as determined using a study-specific questionaire. Acceptability score of equal to or less than 30 out of a possible total of 40 points (75%) is required to deem the procedure ‘feasible’.
Timepoint [4] 414743 0
3 months after stroke.
Secondary outcome [5] 414744 0
Feasibility (assessed as a composite secondary outcome): Ability to record non-invasive ICP before and after lumbar puncture as determined using patient medical records.
Timepoint [5] 414744 0
Immediately before and after lumbar puncture.
Secondary outcome [6] 414745 0
Exploratory outcomes: infarct growth at 24 hours as determined using either MRI or non-contrast CT head scan and computed tomographic angiogram (CTA).
Timepoint [6] 414745 0
24 hours after commencement of stroke symptoms.
Secondary outcome [7] 414746 0
Exploratory outcomes: proportion of patients achieving early clinical improvement using the NIHSS score.
Timepoint [7] 414746 0
24 hours after lumbar puncture.
Secondary outcome [8] 414747 0
Exploratory outcomes: proportion of patients with mRS 0-2 at 3 months.
Timepoint [8] 414747 0
3 months after stroke.
Secondary outcome [9] 414749 0
Exploratory outcomes: difference in nICP at time of lumbar puncture and 1-3 days after stroke as determined using transcranial Doppler ultrasound and non-invasive peripheral arterial waveform monitoring.
Timepoint [9] 414749 0
At time of lumbar puncture and 1-3 days after stroke.
Secondary outcome [10] 414750 0
Scientific outcomes (assessed as a composite secondary outcome): compositional analysis of CSF and serum using mass spectromtery.
Timepoint [10] 414750 0
24 hours after commencement of stroke symptoms.

Eligibility
Key inclusion criteria
1. Patients with acute ischaemic stroke confirmed on clinical and imaging criteria with onset (or time last known to be well) within 24 hours.
2. Patient’s age is greater than or equal to 18 years of age.
3. Premorbid mRS is less than or equal to 3.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients on anticoagulants and/or taking any antithrombotic agents (e.g., aspirin, clopidogrel). Patients taking any anticoagulant in the last 48 hours or warfarin within the last 5 days at any dose.
2. Known bleeding diathesis and/or platelet count <100,000.
3. Patients who have received a thrombolytic agent in the previous 72 hours or are planned to receive a thrombolytic agent.
4. Intracranial haemorrhage (ICH) or other non-stroke diagnosis to explain the symptoms (e.g., tumour), or any intracranial space-ocupying lesion that could pose a risk of brain herniation identified by baseline imaging.
5. Basilar artery occlusion or posterior circulation stroke.
6. Pre-stroke mRS of >2 (indicating significant previous disability).
7. Any terminal illness such that patient would not be expected to survive more than 1 year.
8. Any condition that, in the judgement of the investigator could impose hazards to the patients if study therapy is initiated or affect the participation of the patient in the study.
9. Local skin infection at lumbar puncture site, or known spinal defect likely to impede lumbar puncture, e.g., significant scoliosis.
10. Patients with cognitive impairment as per treating neurologist.
11. Clinically evident pregnant women.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Exploratory outcome analyses will be carried out according to standard statistical principles for comparison of parametric or non-parametric distributions as appropriate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/09/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/03/2028
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23371 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 38756 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 312432 0
Commercial sector/Industry
Name [1] 312432 0
CSL
Country [1] 312432 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive, Callaghan
NSW 2308
Country
Australia
Secondary sponsor category [1] 315473 0
None
Name [1] 315473 0
Address [1] 315473 0
Country [1] 315473 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311779 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 311779 0
HNE Research Office, Locked Bag 1, New Lambton NSW 2305
Ethics committee country [1] 311779 0
Australia
Date submitted for ethics approval [1] 311779 0
27/02/2023
Approval date [1] 311779 0
29/03/2023
Ethics approval number [1] 311779 0
2023/ETH00210

Summary
Brief summary
When an ischaemic stroke occurs and a major artery is blocked with a clot, some blood flow is re-routed to the stroke site via ‘bypass’ blood vessels (called collateral vessels) in order to prevent more brain cells from dying. Failure of these bypass vessels mean a stroke can continue to expand and the damage to the brain gets worse. Increased pressure in the skull, which occurs after stroke, can cause failure of these bypass vessels and thus make a stroke worse.

We hypothesise that by removing some cerebrospinal fluid (the fluid that surrounds your brain) we can prevent pressure elevation after a stroke and therefore make the stroke less severe. The first thing we have to do is check whether we can safely take some cerebrospinal fluid from stroke patients. That is what this trial is designed to look at, whether we can safely take some cerebrospinal fluid from stroke patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122334 0
Prof Neil Spratt
Address 122334 0
Medical Sciences Building, University of Newcastle, Callaghan, NSW, 2308
Country 122334 0
Australia
Phone 122334 0
+61 02 49217402
Fax 122334 0
Email 122334 0
[email protected]
Contact person for public queries
Name 122335 0
Kirsten Coupland
Address 122335 0
Medical Sciences Building, University of Newcastle, Callaghan, NSW, 2308
Country 122335 0
Australia
Phone 122335 0
+61 02 40421611
Fax 122335 0
Email 122335 0
[email protected]
Contact person for scientific queries
Name 122336 0
Dr. Kirsten Coupland
Address 122336 0
Medical Sciences Building, University of Newcastle, Callaghan, NSW, 2308
Country 122336 0
Australia
Phone 122336 0
+61 02 40421611
Fax 122336 0
Email 122336 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data collected during the trial, after de-identification. All individual participant data collected during the trial will be available. Data shared will be dependent on the request.
When will data be available (start and end dates)?
Immediately after patient enrolment with no end date.
Available to whom?
Only researchers who provide a methodologicall sound proposal.
Available for what types of analyses?
Studies of a similar nature.
How or where can data be obtained?
Access subject to approval by Principal Investigator (Prof. Neil Spratt; [email protected]).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18915Study protocol  [email protected]
19955Ethical approval  [email protected]



Results publications and other study-related documents

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