Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000713493p
Ethics application status
Submitted, not yet approved
Date submitted
6/06/2025
Date registered
7/07/2025
Date last updated
7/07/2025
Date data sharing statement initially provided
7/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
The Biological Rationale for Arginine vasopressin Versus Opinion (BRAVO) study: comparing effectiveness of two commonly used regimes of arginine vasopressin infusion when used with norepinephrine in treatment of hypotension.
Scientific title
A Pilot Pragmatic Study to assess the Effectiveness of two different AVP infusions regimes when used with Norepinephrine in hypotension: The BRAVO (Biological Rationale for AVP Versus Opinion) study
Secondary ID [1] 314605 0
nil known
Universal Trial Number (UTN)
U1111-1323-9396
Trial acronym
BRAVO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hypotension 337737 0
shock 337738 0
sepsis 337739 0
cardiogenic shock 337740 0
Condition category
Condition code
Emergency medicine 334063 334063 0 0
Resuscitation
Cardiovascular 334064 334064 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Once shock, hypotension and a need for any pressor is recognised - start Arginine Vasopressin (AVP) at 0.04 U/min as a continuous intravenous infusion as soon as possible – ideally within 4 hours. If not already commenced intravenous infusion of norepinephrine (NE) can be added and titrated to Mean Arterial Pressure (MAP) of >65 mmHg or target MAP defined by clinician. The route is preferably through a central line, but as per local practice can be briefly administered through a proximal peripheral line

The clinician prescribing the infusions is the Emergency Medicine or Intensive Care doctor managing the patient. The clinician administering the medication is the Emergency or ICU nurse. The adherence to protocol will be assessed by the electronic medical record medication record that is recorded at every change of rate or dose and at least once an hour.
If NE requirement is, or becomes, nil, continue AVP after cessation of NE, and review MAP and clinical perfusion markers. wean AVP in decrements of 0.01 U/min according to clinician preference.
Intervention code [1] 331233 0
Treatment: Drugs
Comparator / control treatment
Once shock, hypotension and a need for any pressor is recognised: commence Norepinephrine (NE) at clinicians preferred rate. As per the opinion in the form of the 'unguided statement' of the panel of the Surviving Sepsis Committee Guidelines - once NE rate exceeds 0.019 mic/kg/min start Arginine Vasopressin (AVP) at 0.04 U/min.

The clinician prescribing the infusions is the Emergency Medicine or Intensive Care doctor managing the patient. The clinician administering the medication is the Emergency or ICU nurse. The adherence to protocol will be assessed by the electronic medical record medication record that is recorded at every change of rate or dose and at least once an hour.

Continue at that rate until NE requirement is consistently below < 0.2 mic/kg/min and definitely cease AVP when NE dose rate is below 0.15 mic/kg/min. The manner in which the clinician ceases or reduced AVP is up to clinician preference.

NE rate may need to increase at this point, and it is up to the clinician if they wish to re-start AVP for a period at a rate of at least 0.01U/min.
Control group
Active

Outcomes
Primary outcome [1] 341724 0
total duration of pressor requirement
Timepoint [1] 341724 0
in retrospect from EMR during the patient's intensive care stay
Secondary outcome [1] 448536 0
Continuous Renal Replacement Therapy requirement as documented in EMR
Timepoint [1] 448536 0
during ICU stay
Secondary outcome [2] 448537 0
death in hospital
Timepoint [2] 448537 0
before discharge and any time within 6 months of discharge
Secondary outcome [3] 448538 0
length of stay intensive care
Timepoint [3] 448538 0
during ICU stay
Secondary outcome [4] 448539 0
length of stay in hospital
Timepoint [4] 448539 0
during hospital stay
Secondary outcome [5] 448540 0
occurrence of Atrial Fibrillation or Ventricular Fibrillation - assessed as a composite event
Timepoint [5] 448540 0
during the ICU stay
Secondary outcome [6] 448541 0
cost of intervention drugs
Timepoint [6] 448541 0
during ICU stay
Secondary outcome [7] 448765 0
adherence and acceptability of the protocol
Timepoint [7] 448765 0
adherence during the ICU stay, and within one week of the end of the trial
Secondary outcome [8] 448767 0
total fluid balance at end of ICU stay
Timepoint [8] 448767 0
during ICU stay
Secondary outcome [9] 449225 0
acceptance of the individual protocols by ICU staff and emergency staff - both doctors and nurses
Timepoint [9] 449225 0
ideally before discharge from hospital or at any time within 6 months

Eligibility
Key inclusion criteria
Patients
Adults > 17 years old
AND
Clinicians want to start a vaso-pressor to maintain a prescribed Mean Arterial Pressure (MAP).
AND
Clinician wants an arterial line to monitor MAP
(A diagnosis of sepsis or cardiogenic shock is not required, just that clinician requires a MAP and requires some pressor to achieve it – arterial access is mandatory, and central access is recommended, and mandatory after 12 hours if pressors still required. Initial use of proximal peripheral line acceptable. There is no requirement to have achieved a specific fluid load and all other interventions are up to the clinician).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinician does not want to use AVP at any time
2. Acute mesenteric ischaemia recognised
3. Acute limb ischaemia recognised
4. Acute myocardial infact type 1 requiring intervention

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)
Griffith University Clinical Trials Unit Randomisation Service: An automated 24-hour randomisation service is available for investigators to use via a web portal
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a pilot trial component of a Pragmatic study, designed to assess adherence to a protocol, acceptability of the intervention, and selection of the most appropriate outcome in a future trial, and to assess any signal of difference in duration of pressor. We propose to recruit 100 patients in this pilot phase.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/07/2025
Actual
Date of last participant enrolment
Anticipated
1/06/2026
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 28010 0
Sunshine Coast University Hospital - Birtinya
Recruitment postcode(s) [1] 44213 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 319164 0
Charities/Societies/Foundations
Name [1] 319164 0
Sunshine Coast Hospital and Health Service Wishlist-SERTF Research Grant
Country [1] 319164 0
Australia
Funding source category [2] 319217 0
Hospital
Name [2] 319217 0
sunshine coast university hospital Intensive Care Unit internal research fund
Country [2] 319217 0
United Kingdom
Primary sponsor type
Hospital
Name
Sunshine Coast University Hospital
Address
Country
Australia
Secondary sponsor category [1] 321622 0
Charities/Societies/Foundations
Name [1] 321622 0
Sunshine Coast Hospital and Health Service Wishlist-SERTF Research Grant
Address [1] 321622 0
Country [1] 321622 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317744 0
Metro North Health Human Research Ethics Committee A
Ethics committee address [1] 317744 0
Ethics committee country [1] 317744 0
Australia
Date submitted for ethics approval [1] 317744 0
03/03/2025
Approval date [1] 317744 0
Ethics approval number [1] 317744 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142010 0
A/Prof peter garrett
Address 142010 0
Sunshine Coast University Hospital, Intensive Care Unit, 6 Doherty street, Birtinya, QLD 4575
Country 142010 0
Australia
Phone 142010 0
+61 0438764878
Fax 142010 0
Email 142010 0
[email protected]
Contact person for public queries
Name 142011 0
peter garrett
Address 142011 0
Sunshine Coast University Hospital, Intensive Care Unit, 6 Doherty street, Birtinya, QLD 4575
Country 142011 0
Australia
Phone 142011 0
+61 0438764878
Fax 142011 0
Email 142011 0
[email protected]
Contact person for scientific queries
Name 142012 0
peter garrett
Address 142012 0
Sunshine Coast University Hospital, Intensive Care Unit, 6 Doherty street, Birtinya, QLD 4575
Country 142012 0
Australia
Phone 142012 0
+61 0438764878
Fax 142012 0
Email 142012 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
At the end of the study
To:
A finite period of: 10 years
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
No


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.