Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001405707p
Ethics application status
Submitted, not yet approved
Date submitted
24/10/2022
Date registered
2/11/2022
Date last updated
2/11/2022
Date data sharing statement initially provided
2/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Milrinone infusion for cerebral vasospasm in aneurysmal sub-arachnoid haemorrhage patients: a pilot randomised controlled study
Scientific title
Milrinone infusion for cerebral vasospasm in aneurysmal sub-arachnoid haemorrhage patients: a pilot randomised controlled study
Secondary ID [1] 308247 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cerebral vasospam 328035 0
aneurysmal sub-arachnoid haemorrhage 328036 0
Condition category
Condition code
Stroke 325093 325093 0 0
Haemorrhagic
Neurological 325114 325114 0 0
Other neurological disorders
Cardiovascular 325115 325115 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will be continuous intravenous milrinone infusion, for up to 7 days. To commence at time of radiological diagnosis of vasospasm at an initial dose of 0.25mcg/kg/min. Titrated to a maximum of 0.75mcg/kg/min as tolerated. This will be in addition to standard care which will consist of induced hypertension, with fluid therapy and noradrenaline infusion as directed by the treating clinician. Oral nimodipine at a dose of 60mg every 4hours will also be prescribed as part of standard therapy.
Intervention code [1] 324712 0
Treatment: Drugs
Comparator / control treatment
Standard care will consist of induced hypertension, with fluid therapy and noradrenaline infusion as directed by the treating clinician. Oral nimodipine at a dose of 60mg every four hours will also be prescribed as part of standard therapy.
Control group
Active

Outcomes
Primary outcome [1] 332903 0
total dose of milrinone administered over 7 days as recorded in the medical record
Timepoint [1] 332903 0
Monitored continuously for up to 7 days post commencement
Primary outcome [2] 332932 0
total duration of milrinone administration up to 7 days as recorded in the medical record
Timepoint [2] 332932 0
monitored continuously for up to 7 days from commencement
Secondary outcome [1] 415059 0
vasopressor requirement from the medical record
Timepoint [1] 415059 0
monitored continuously for up to 7 days from commencement
Secondary outcome [2] 415060 0
incidence of adverse events:
- clinically significant hypotension via invasive arterial monitoring
- clinically significant tachycardia or arrhythmia via continuous cardiac monitoring
- Hypokalaemia < 3.0mmol/L on routine blood gas monitoring
The definition of 'clinically significant' will be 'deemed to require intervention by the treating clinician'
Timepoint [2] 415060 0
hypotension and tachycardia/arrhythmia are continuously monitored in the ICU
Blood gas monitoring is routinely performed at 4-6hrly intervals.

Incidence of adverse events will be captured for 7 days following the radiological diagnosis of vasospasm
Secondary outcome [3] 415061 0
incidence of radiological resolution of vasospasm via CT angiogram or formal angiography as directed by the treating clinician
Timepoint [3] 415061 0
The frequency of radiological assessment of vasospasm will be at the discretion of the treating clinician, based on the clinical course of the patient but must occur at least once during the 7-day period following diagnosis

Eligibility
Key inclusion criteria
Adults
Admitted to ICU
Radiologically confirmed vasospam
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Whole territory cerebral infarction in the vasospasm territory on CT scan
Cardiac failure requiring inotropic support
Pregnancy
Any contraindication to milrinone

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



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is a pilot study designed to explore the safety and feasibility of a standard ICU therapy in a novel setting. A sample of 40 patients (20 in each arm) will be taken.

A single, planned interim analysis will be conducted with data from the first 20 participants to assess safety and feasibility.

Data collected will include baseline demographic and physiological data. Comparison between groups will be performed using chi-squared tests for categorical variables and Student’s t-test or Mann-Whitney U test for parametric and non-parametric variables respectively. Continuous data will be presented as means with standard deviations or medians with interquartile ranges as appropriate. Comparisons will be presented as relative risks with point estimates and 95% confidence intervals. Statistical significance will be defined as a p value less than 0.05 for all tests

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/02/2023
Actual
Date of last participant enrolment
Anticipated
1/10/2024
Actual
Date of last data collection
Anticipated
8/10/2024
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23436 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 38838 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 312504 0
Hospital
Name [1] 312504 0
Monash Medical Centre
Country [1] 312504 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre
Address
246 Clayton Road
Clayton 3168
Victoria
Country
Australia
Secondary sponsor category [1] 314092 0
None
Name [1] 314092 0
Address [1] 314092 0
Country [1] 314092 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 311840 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 311840 0
246 Clayton Road
Clayton 3168
Victoria
Ethics committee country [1] 311840 0
Australia
Date submitted for ethics approval [1] 311840 0
25/10/2022
Approval date [1] 311840 0
Ethics approval number [1] 311840 0

Summary
Brief summary
Background: Cerebral vasospasm is a relatively common complication following aneurysmal subarachnoid haemorrhage (aSAH), which is associated with significant morbidity and mortality. Current treatment options to treat cerebral vasospasm are limited. Intravenous milrinone infusion is a potentially promising treatment with a relatively low incidence of adverse effects however, has not been explored in a randomized controlled trial.

Aim: This will be a pilot study to determine the safety and feasibility of intravenous milrinone infusion as a treatment for cerebral vasospasm following aSAH compared to current standard therapy.

Hypothesis: Intravenous milrinone will be a feasible treatment option in the management of cerebral vasospasm following aSAH

Methods: The proposed study is a pilot study trialling intravenous milrinone infusion in patients with radiographically confirmed cerebral vasospasm following aSAH. 20 patients will be allocated to receive IV milrinone alongside standard therapy. A control group of 20 patients will receive standard therapy alone. The primary outcome measured will include the dose and duration of milrinone infusion. Secondary outcomes will include the incidence of adverse events, the resolution of cerebral vasospasm on CT or digital-subtraction angiography (DSA) and the vasopressor requirement.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122554 0
Dr Adrian Pakavakis
Address 122554 0
Monash Medical Centre
246 Clayton Road
Clayton 3168
Victoria
Country 122554 0
Australia
Phone 122554 0
+61 3 9594 3277
Fax 122554 0
Email 122554 0
adrian.pakavakis@monashhealth.org
Contact person for public queries
Name 122555 0
Ms Alice Li
Address 122555 0
Monash Medical Centre
246 Clayton Road
Clayton 3168
Victoria
Country 122555 0
Australia
Phone 122555 0
+61 3 9594 3296
Fax 122555 0
Email 122555 0
alice.li@monash.edu
Contact person for scientific queries
Name 122556 0
Ms Alice Li
Address 122556 0
Monash Medical Centre
246 Clayton Road
Clayton 3168
Victoria
Country 122556 0
Australia
Phone 122556 0
+61 3 9594 6666
Fax 122556 0
Email 122556 0
alice.li@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.