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Trial registered on ANZCTR


Registration number
ACTRN12618001932257p
Ethics application status
Not yet submitted
Date submitted
8/11/2018
Date registered
28/11/2018
Date last updated
28/11/2018
Date data sharing statement initially provided
28/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pentoxyfilline for Reduction of Delayed Cerebral Ischaemia after Aneurysmal Subarachnoid Haemorrhage: a pilot study
Scientific title
Pentoxyfilline for Reduction of Delayed Cerebral Ischaemia after Aneurysmal Subarachnoid Haemorrhage: a pilot study
Secondary ID [1] 296552 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PRECISE-SAH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Delayed Cerebral Ischaemia 310336 0
Subarachnoid haemorrhage 310337 0
Condition category
Condition code
Neurological 309068 309068 0 0
Other neurological disorders
Cardiovascular 309285 309285 0 0
Other cardiovascular diseases
Stroke 309294 309294 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pentoxifylline, 200mg enterally by mouth or nasogastric tube, every 4 hours, for 28 days after aneurysmal subarachnoid haemorrhage.
Adherence will be checked by reviewing the electronic medication prescribing chart to see if the patient has received the medication.
Intervention code [1] 312859 0
Treatment: Drugs
Comparator / control treatment
Placebo
Glucose syrup with food dye to make it look like the medication
Control group
Placebo

Outcomes
Primary outcome [1] 308036 0
Incidence of delayed cerebral ischaemia as measured by CT scan or MRI afteraneurysmal subarachnoid haemorrhage.
Timepoint [1] 308036 0
single assessment at 6 weeks after the initial haemorrhage.
Secondary outcome [1] 353771 0
Modified Rankin Scale score
Timepoint [1] 353771 0
90 days after the initial haemorrhage.
Secondary outcome [2] 353772 0
Mortality rate
Timepoint [2] 353772 0
90 days post-haemorrhage
Secondary outcome [3] 353773 0
Rate of new intracranial haemorrhage after initial aneurysmal subarachnoid haemorrhage assessed by neuroimaging with either CT scan or MRI.
Timepoint [3] 353773 0
6 weeks post-haemorrhage.
Secondary outcome [4] 353774 0
Rate of adverse events reported by patients on from hospital data. Patient records will be assessed at the same time as the 90 day assessment if being conducted to check for adverse events.
Adverse events can include: Common (>1%) nausea, vomiting, dizziness, headache, flushing; Infrequent (0.1–1%) angina, palpitations; Rare (<0.1%) hypersensitivity, itching, rash, urticaria, bleeding, hallucinations, arrhythmias, aseptic meningitis
Timepoint [4] 353774 0
6 weeks post-haemorrhage.

Eligibility
Key inclusion criteria
1. Adults (>18yr of age)
2. Admitted to Intensive Care Unit
3. Diagnosis of aneurysmal subarachnoid haemorrhage (aSAH).
4. High-grade aSAH with high chance of developing vasospasm: WFNS grade 4 or 5 regardless of Fisher score (VASOGRADE: Red).
5. Patients found to have vasospasm on screening angiography done within first week post ictus regardless of aSAH classification.
6. Within 4 days of ictus.
7. Culprit aneurysm that has been secured with either Interventional Neuroradiology (coiling) or neurosurgery (clipping)
8. Assessment by proceduralist (INR or neurosurgeon) that the aneurysm has been sufficiently secured.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. SAH not from aneurysm (trauma, AVM, etc.).
2. Coexistent neurological vascular injury (extradural, subdural haemoatoma).
3. Patients on antiplatelet medications or anticoagulation (NOAC, heparin, etc.) including those that receive a stent
4. Expected to die within this admission.
5. Allergy to pentoxifylline or xanthines.
6. Unable to use enteral route.
7. Pregnant or breastfeeding patients.
8. Liver dysfunction with AST and/or ALT >500
9. Renal dysfunction with eGFR <30ml/hr

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be randomised to receive pentoxifylline or placebo on a 1:1 ratio according to an online generated randomisation list. A member of the ICU staff independent to the study will create the randomisation list and deliver it securely to the compounding pharmacy making the study drugs. The compounding pharmacy will be instructed to make and label sequentially the study medication and allocate pentoxifylline or placebo depending on the randomisation list. Study pack will be made which will contain enough medication for 1 patient for 28 days.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Online generated randomisation list.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
For the primary outcome, data will be treated as categorical versus categorical with a non-parametric distribution. This would require analysis with Fisher’s exact. A P-value of <0.05 would be considered as a statistically significant difference.

For the secondary outcomes all data would be considered to have a non-parametric distribution.

For modified Rankin Scale score at 90 days data results would be dichotomized and a score of 0 to 3 would be considered a poor outcome and a score of 4 to 6 would be considered a good outcome. Therefore, with categorical versus categorical data, Fisher’s exact test would be used. A P-value of <0.05 would be considered as a statistically significant difference.

For mortality rate at 90 days and the rate of new intracranial haemorrhage after initial aSAH, the medians of 2 groups will be compared. Given the numerical versus categorical data Mann-Whitney U test would be used for both analyses. A P-value of <0.05 would be considered as a statistically significant difference.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 12375 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 24638 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 301131 0
Hospital
Name [1] 301131 0
John Hunter Hospital
Address [1] 301131 0
Lookout Road, New Lambton Heights, NSW, 2305
Country [1] 301131 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Lookout Road, New Lambton Heights, NSW, 2305
Country
Australia
Secondary sponsor category [1] 300753 0
None
Name [1] 300753 0
Address [1] 300753 0
Country [1] 300753 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 301882 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 301882 0
John Hunter Hospital, Lookout Road, New Lambton Heights, NSW, 2305
Ethics committee country [1] 301882 0
Australia
Date submitted for ethics approval [1] 301882 0
11/02/2019
Approval date [1] 301882 0
Ethics approval number [1] 301882 0

Summary
Brief summary
Pentoxifylline is a medication that decreases the viscosity of blood and helps red blood cells travel better through narrow blood vessels. Aneurysmal subarachnoid haemorrhage is a type of stroke that can be complicated by a second type of stroke called delayed cerebral ischaemia. This is a pilot, randomized controlled study to determine if pentoxifylline when used in aneurysmal subarachnoid haemorrhage decreases the rate of delayed cerebral ischaemia.
Trial website
Nil known
Trial related presentations / publications
None yet
Public notes

Contacts
Principal investigator
Name 88426 0
Dr F. Eduardo Martinez, FCICM
Address 88426 0
John Hunter Hospital, Lookout Road, New Lambton Heights, NSW, 2305
Country 88426 0
Australia
Phone 88426 0
+61 249214241
Fax 88426 0
Email 88426 0
ed.martinez@hnehealth.nsw.gov.au
Contact person for public queries
Name 88427 0
Dr F. Eduardo Martinez, FCICM
Address 88427 0
John Hunter Hospital, Lookout Road, New Lambton Heights, NSW, 2305
Country 88427 0
Australia
Phone 88427 0
+61 249214241
Fax 88427 0
Email 88427 0
ed.martinez@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 88428 0
Dr F. Eduardo Martinez, FCICM
Address 88428 0
John Hunter Hospital, Lookout Road, New Lambton Heights, NSW, 2305
Country 88428 0
Australia
Phone 88428 0
+61 249214241
Fax 88428 0
Email 88428 0
ed.martinez@hnehealth.nsw.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
When will data be available (start and end dates)?
When results published, data will be available immediately following publication for 5 years.
Available to whom?
Anyone
Available for what types of analyses?
Any
How or where can data be obtained?
By request to the chief investigator
What supporting documents are/will be available?
Study protocol
Summary results
No Results