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Trial registered on ANZCTR


Registration number
ACTRN12620000280909p
Ethics application status
Not yet submitted
Date submitted
29/01/2020
Date registered
3/03/2020
Date last updated
3/03/2020
Date data sharing statement initially provided
3/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of resuscitation in patients with sepsis using a novel ultrasound measurement (delta-carotid velocity time integral) to determine intravascular fluid replacement
Scientific title
Using the Delta Carotid Velocity Time Integral to Determine Volume Responsiveness in Adult Patients with Sepsis
Secondary ID [1] 300357 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 315984 0
Condition category
Condition code
Emergency medicine 314261 314261 0 0
Resuscitation
Infection 314517 314517 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Design: Prospective cohort study, diagnostic test study
Location: St Vincent's Hospital, Melbourne
Recruitment: opportunistic
Exposure arm: positive delta carotid velocity time integral (positive delta-cVTI)
Comparative arm: negative delta carotid velocity time interval (negative delta-cVTI)

Patients meeting the inclusion criteria will be recruited in to the study by a study investigator, and the study protocol will run in parallel to standard clinical care. Participants will have a standard set of observations performed. Participants will have ultrasound measurements performed by echocardiography trained clinicians. Participants will then have a left ventricular outflow tract velocity time integral (LVOT VTI) measurement performed using the phased ultrasound probe, with a 5 chamber view, while lying on the bed with the head elevated to 45 degrees. Using the linear probe, the right carotid diameter 1-2cm below the carotid bifurcation will be measured and recorded, the probe will be rotated 90degrees from diameter measurement and use pulsed wave doppler to calculate the carotid VTI, and carotid VTI respiratory variation.
The ultrasound site used will be marked with a marker. The patient will then be placed in the supine position with the legs elevated to 45 degrees. Using the same approach detailed above the LVOT VTI and cVTI will be remeasured. Participants will the be returned to the original lying, head-up position and given a 500ml bolus of crystalloid as per standard clinical care. Another set of standard observations will be taken and a repeat LVOT VTI and cVTI measured.
All ultrasound images will be recorded by the scanning investigator in an anonymised fashion using their study number. Images will be reviewed and the change (delta) in carotid VTI and change in LVOT VTI and each stage will be calculated be a separate investigator, to minimise bias and ensure ultrasound image quality.
We expect the protocol to take 30 minutes to complete per patient.
Intervention code [1] 316650 0
Diagnosis / Prognosis
Intervention code [2] 316651 0
Early detection / Screening
Intervention code [3] 316652 0
Treatment: Other
Comparator / control treatment
The comparator group is defined as negative delta carotid velocity time interval (negative delta-cVTI). The comparator will proceed with the identical study protocol and be retrospectively assigned to the their respective arm with the results of the LVOT VTI. This is to prevent bias from arm allocation as both delta-LVOT VTI and delta-cVTI measurements are performed simultaneously.
Control group
Active

Outcomes
Primary outcome [1] 322652 0
Ultrasound determined carotid velocity time integral sensitivity and specificity
Timepoint [1] 322652 0
Approximately 30 minutes following protocol commencement
Primary outcome [2] 322678 0
Ultrasound measured carotid blood flow sensitivity and specificity
Timepoint [2] 322678 0
Approximately 30 minutes following protocol commencement
Primary outcome [3] 322679 0
Ultrasound measured carotid respiratory variation
Timepoint [3] 322679 0
Approximately 30 minutes following protocol commencement
Secondary outcome [1] 379187 0
Clinical volume responsiveness, determined by at least 10% improvement in heart rate (HR) or blood pressure (BP). Both of these vital signs will be recorded by the emergency trained nurse before and after the intervention. HR will be recorded by counting the radial pulse for 60 min and BP will be recorded using standardised automatic hospital machine.
Timepoint [1] 379187 0
Approximately 30 minutes following protocol commencement

Eligibility
Key inclusion criteria
1) Working diagnosis of sepsis*

*Surviving sepsis 2016 definition:
Potential source of infection with 2 of:
- SBP < /= 100
- RR >/= 22
- GCS < 15

2) >/= 18y/o
3) Sinus Rhythm
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Treating clinician determined contra-indication to fluid challenge
2) Concurrent vasopressin use
3) Pregnancy
4) Cardiac arrest due to severe hypotension or sepsis
5) Clinical hypervolaemia
- decompensated chronic liver disease with ascites
- nephrotic syndrome
- severe cardiomyopathy with evidence of fluid overload (elevated JVP, bilateral pedal oedema, bibasal creps)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Power 80%, alpha 0.05
87 patients, with 2 tier 10% dropout / exclusion
Final sample size 35 per group
Analysis of sensitivity and sensitivity as outcome measure

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)
VIC
Recruitment hospital [1] 15691 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 29111 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 304780 0
Hospital
Name [1] 304780 0
St Vincent's Hospital
Address [1] 304780 0
41 Victoria Parade,
Fitzroy
VIC
3065
Country [1] 304780 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's hospital Melbourne
Address
Research Centre (Epicentre)
Emergency Department
41 Victoria Parade
Fitzroy
VIC
3065
Country
Australia
Secondary sponsor category [1] 305113 0
None
Name [1] 305113 0
Address [1] 305113 0
Country [1] 305113 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 305196 0
St Vincent's Hospital Ethics Commitee
Ethics committee address [1] 305196 0
Research Department
HREC Committee
41 Victoria Parade
Fitzroy
Victoria 3065
Ethics committee country [1] 305196 0
Australia
Date submitted for ethics approval [1] 305196 0
01/04/2020
Approval date [1] 305196 0
Ethics approval number [1] 305196 0

Summary
Brief summary
This modified prospective cohort style study design will aim to analyse and validate the use of the delta-carotid velocity time integral to predict volume responsiveness in sepsis.
Appropriate volume resuscitation is a hallmark of emergency medicine practice. Optimal volume resuscitation is often complex and increasingly controversial, with wide discrepancies in practice and guidelines. A large spectrum of guidelines exist on the ‘ideal’ fluid resuscitation, the majority focusing on sepsis. The current Surviving Sepsis guidelines recommend aggressive high volume fluid resuscitation in sepsis induced hypoperfusion . Other guideline range from high volume fluid resuscitation in all sepsis patients , to a fluid challenge in septic shock only .
Our study will focus on the emergency department population, with an aim to validate this test allowing use in clinical practise. We will address the critique of high patient heterogeneity in previous studies by focusing on emergency department patients with a working diagnosis of sepsis. We propose that determining optimal intravascular filling and the timing of vasopressor use would be the most frequent clinical application of this test in clinical practice, especially given current controversies in the agreed optimal fluid resuscitation of these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99570 0
Dr Hamed Akhlaghi
Address 99570 0
St Vincent's Hospital
41 Victoria Parade
Fitzroy
VIC
3065
Country 99570 0
Australia
Phone 99570 0
+61 421981487
Fax 99570 0
Email 99570 0
hamed.akhlaghi@svha.org.au
Contact person for public queries
Name 99571 0
Dr Hamed Akhlaghi
Address 99571 0
St Vincent's Hospital
41 Victoria Parade
Fitzroy
VIC
3065
Country 99571 0
Australia
Phone 99571 0
+61 421981487
Fax 99571 0
Email 99571 0
hamed.akhlaghi@svha.org.au
Contact person for scientific queries
Name 99572 0
Dr Matthew Kilmurray
Address 99572 0
St Vincent's Hospital
41 Victoria Parade
Fitzroy
VIC
3065
Country 99572 0
Australia
Phone 99572 0
+61 406285770
Fax 99572 0
Email 99572 0
matthew.kilmurray@svha.org.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 de-identified IPD collated in accordance with the protocol.
When will data be available (start and end dates)?
Data available immediately following publication, with no end date.
Available to whom?
Requesting clinicians on request assessed on a case by case basis.
Available for what types of analyses?
Available for meta-analysis
How or where can data be obtained?
From direct contact with the PI via the email address: hamed.akhlaghi@svha.org.au
What supporting documents are/will be available?
Study protocol
Clinical study report
Ethical approval
How or where can supporting documents be obtained?
Type [1] 6619 0
Ethical approval
Citation [1] 6619 0
Link [1] 6619 0
Email [1] 6619 0
hamed.akhlaghi@svha.org.au
Other [1] 6619 0
Attachment [1] 6619 0
Type [2] 6869 0
Study protocol
Citation [2] 6869 0
Link [2] 6869 0
Email [2] 6869 0
hamed.akhlaghi@svha.org.au
Other [2] 6869 0
Attachment [2] 6869 0
Type [3] 6870 0
Clinical study report
Citation [3] 6870 0
Link [3] 6870 0
Email [3] 6870 0
hamed.akhlaghi@svha.org.au
Other [3] 6870 0
Attachment [3] 6870 0
Summary results
No Results