Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001055796p
Ethics application status
Submitted, not yet approved
Date submitted
15/07/2022
Date registered
29/07/2022
Date last updated
1/08/2022
Date data sharing statement initially provided
29/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
HypErtensive Augmentation During acute ischaemic STroke Assisting Reperfusion Therapies
Scientific title
HypErtensive Augmentation with metaraminol During acute ischaemic STroke Assisting Reperfusion Therapies
Secondary ID [1] 307586 0
None
Universal Trial Number (UTN)
None
Trial acronym
HEAD-START 2
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Acute Ischaemic Stroke 327030 0
Condition category
Condition code
Stroke 324202 324202 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who meet trial inclusion criteria (hemispheric stroke symptoms with initial blood pressure below 160mmHg on presentation) will be consented for blood pressure augmentation with Metaraminol prior to definitive intervention for acute ischaemic stroke.

After initial multimodal CT perfusion imaging, blood pressure is measured every 90 secondly with bolus intravenous metaraminol administration via 'chooks foot' infusion device, aiming for systolic blood pressure (sBP) of 160-180mmHg.

If sBP is 150-159mmHg, 0.1mg of intravenous bolus metaraminol is administered
If sBP is 130-149mmHg, 0.15mg of intravenous bolus metaraminol is administered
If sBP is 110-129mmHg, 0.25mg of intravenous bolus metaraminol is administered
If sBP is less than 110mmHg, 0.5mg of intravenous bolus metaraminol is administered

Metaraminol will be administered every 90 seconds for a maximum of 7.5 minutes or until target sBP is reached.

Intravenous Labetalol will be administered at 5-10mg bolus doses if sBP is above target range as determined by planned intervention. The maximum total labetalol dose administered will depend on patient heart rate and tolerability of labetalol.

Repeat CT perfusion imaging is performed after 7.5 minutes of blood pressure augmentation with metaraminol and blood pressure measurement. Repeat NIHSS (National Institutes of Health Stroke Scale) is performed after completion of CT perfusion imaging.
Intervention code [1] 324034 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332018 0
Change in cerebral blood flow post-BP augmentation with metaraminol as demonstrated by CT perfusion imaging
Timepoint [1] 332018 0
Baseline (pre-intervention) and 7.5 minutes post-blood pressure augmentation with metaraminol
Secondary outcome [1] 411911 0
Change in neurologic function as assessed with the National Institutes of Health Stroke Scale (NIHSS) post-blood pressure augmentation with metaraminol
Timepoint [1] 411911 0
Baseline (pre-intervention), Post-repeat CT Perfusion imaging, approximately 9 minutes post-blood pressure augmentation with metaraminol

Eligibility
Key inclusion criteria
1) Acute anterior circulation ischaemic stroke with measurable neurologic deficit
2) Demonstration of penumbra of CT perfusion imaging (Delay time (DT) lesion >3 seconds volume > 30 mL, as measured by MiSTAR software)
3) Initial systolic blood pressure on ED presentation below 160mmHg
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Known renal failure (eGFR < 30mL)
2) Iodine contrast hypersensitivity
3) Any contraindication to Metaraminol administration ((hypersensitivity to Metaraminol including sulfite allergy, nonselective Monoamine Oxidase Inhibitor (MAO-I) therapy (phenelzine, tranylcypromine) in the past 14 days))
4) <50 years old
5) Previous intracerebral or subarachnoid haemorrhage
6) Presence of an intracranial aneurysm or arteriovenous malformation
7) Presence of an aortic dissection
8) Presence of an acute or recent (<30 days) myocardial infarction
9) Recent (<1 month) left ventricular failure
10) Any other condition which, in the opinion of the Investigator, increases the risk of blood pressure augmentation

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2022
Actual
Date of last participant enrolment
Anticipated
30/09/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 311857 0
Hospital
Name [1] 311857 0
Royal Adelaide Hospital
Country [1] 311857 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
1 Port Road
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 313331 0
None
Name [1] 313331 0
Address [1] 313331 0
Country [1] 313331 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 311296 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 311296 0
1 Port Road
Adelaide SA 5000
Ethics committee country [1] 311296 0
Australia
Date submitted for ethics approval [1] 311296 0
13/07/2022
Approval date [1] 311296 0
Ethics approval number [1] 311296 0

Summary
Brief summary
In ischaemic stroke (caused by a blocked blood vessel) a region of the brain is starved of oxygen, and dies.

There is a window of opportunity to restore blood flow to prevent tissue death, even small increases in blood flow can lengthen this window.

Only unblocking blocked arteries by clot dissolving medication or sucking the clot out directly are proven therapies. We propose that using Metaraminol to boost blood pressure will improve blood flow to the brain as a bridging method until definitive treatment restores blood flow.

We aim to prove this approach using advanced brain imaging called CT perfusion, which can effectively detect the size and region of brain tissue at threat of dying without blood flow restoration.

Stroke patients are usually managed without blood pressure support, but if our research is positive, this practice could be altered, especially in long distance stroke retrievals.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120610 0
Prof Timothy John Kleinig
Address 120610 0
Department of Neurology, Level 9, Royal Adelaide Hospital, North Terrace, Adelaide, 5000
Country 120610 0
Australia
Phone 120610 0
+61 421832272
Fax 120610 0
Email 120610 0
timothy.kleinig@sa.gov.au
Contact person for public queries
Name 120611 0
Prof Timothy John Kleinig
Address 120611 0
Department of Neurology, Level 9, Royal Adelaide Hospital, North Terrace, Adelaide, 5000
Country 120611 0
Australia
Phone 120611 0
+61 421832272
Fax 120611 0
Email 120611 0
timothy.kleinig@sa.gov.au
Contact person for scientific queries
Name 120612 0
Prof Timothy John Kleinig
Address 120612 0
Department of Neurology, Level 9, Royal Adelaide Hospital, North Terrace, Adelaide, 5000
Country 120612 0
Australia
Phone 120612 0
+61 421832272
Fax 120612 0
Email 120612 0
timothy.kleinig@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Beginning 3 months post-main results publication with no end date determined yet
Available to whom?
To be determined by a case-by-case basis at the discretion of the Primary Investigator
Available for what types of analyses?
To be determined by a case-by-case basis at the discretion of the Primary Investigator
How or where can data be obtained?
Access subject to approval by Principal Investigator, Prof. Timothy Kleinig who can be contacted on +618 7074 0000.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.