Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000199213
Ethics application status
Approved
Date submitted
29/01/2018
Date registered
7/02/2018
Date last updated
3/06/2021
Date data sharing statement initially provided
13/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Paramedic administered antibiotics for patients with severe sepsis: Does this reduce the time to appropriate antibiotic therapy?
Scientific title
Paramedic Antibiotics for Severe Sepsis: A Phase 2 Study
Secondary ID [1] 293902 0
None
Universal Trial Number (UTN)
Trial acronym
The PASS Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 306377 0
Condition category
Condition code
Infection 305463 305463 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention arm - Paramedic administration of 2g intravenous Ceftriaxone sodium for patients with severe sepsis. Compliance with the intervention will be monitored by reconciling all study drug administration through the Ambulance Victoria Pharmacy.
Intervention code [1] 300171 0
Treatment: Drugs
Comparator / control treatment
Control arm - Standard paramedic care of severe sepsis patients. This involves the following: a detailed medical history, relevant clinical exam, insertion of an IV cannula, administration of IV fluids, and transport to an appropriate hospital.
Control group
Active

Outcomes
Primary outcome [1] 304602 0
Time from paramedic arrival at scene to appropriate administration of antibiotics. All relevant times (arrival at scene, arrival at hospital, drug administration) are logged in the electronic medical record. In both arms of the study, the time from paramedic arrival at scene will correspond to t=0. We will then determine the interval between this point and the administration of an antibiotic. In the intervention arm, this will be at the scene. In the control arm, this will be after arrival to hospital.

The appropriateness of the antibiotic administered, will be determined by in vitro susceptibility testing of any pathogens isolated from the patients. E.g. is the pathogen sensitive to the antibiotic. If not, the therapy will be considered inappropriate.
Timepoint [1] 304602 0
Time of administration of first antibiotic. This is clearly documented in the electronic record. the time of arrival of paramedics at the scene will be subtracted from this, such that the interval time to antibiotics can then be calculated.
Secondary outcome [1] 342514 0
Microorganism identified. This will be determined from the laboratory results of cultures obtained pre-hospital.
Timepoint [1] 342514 0
First blood culture. All patients will have a blood culture obtained by paramedics in the pre-hospital setting.
Secondary outcome [2] 342516 0
Infection with microorganism resistant to ceftriaxone. This will be determined from susceptibility testing in the laboratory.
Timepoint [2] 342516 0
First blood culture. All patients will have a blood culture obtained by paramedics in the pre-hospital setting.
Secondary outcome [3] 342517 0
Hospital discharge diagnosis. This will be a free-text entry in the patients hospital discharge documentation, and will be the hospitals view of the patients final diagnosis.
Timepoint [3] 342517 0
Hospital discharge. The final diagnosis will be determined at the time point the patient is discharged from hospital.
Secondary outcome [4] 342518 0
Intensive care unit admission and length of stay. We are interested in determining the proportion of the study cohort that require ICU admission. In those that are admitted to ICU, we will record the length of time they remain there.
Timepoint [4] 342518 0
During hospital admission. We are interested to know if the patient required ICU admission at any point in their hospital stay.
Secondary outcome [5] 376832 0
We are interested in the enrolled patient's functional status post event. The EQ-5D instrument will be used to assess the patient's quality-of-life.
Timepoint [5] 376832 0
Patient follow-up call will be conducted at 90-days post event.

Eligibility
Key inclusion criteria
Patients are eligible to be enrolled in the PASS study if they present with a history suggestive of infection, are greater than or equal to 18 years of age, are transported to a participating hospital, and who meet the following initial paramedic VSS criteria:

• SBP<100mmHg; and
• GCS<15
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Female known to be pregnant
• Suspected or known allergy to any cephalosporin antibiotics (e.g. Ceftriaxone) and confirmed severe allergic reactions to penicillin (e.g. Anaphylaxis or Angio oedema). If unable to confirm severe allergic reactions to penicillin and the patient meets the inclusion criteria (and no other exclusion criteria) enrolment can occur.
• Suspected meningococcal infection (will receive ceftriaxone as standard care)
• Deranged clinical parameters considered likely to be from a non-infective cause (such as dehydration, acute coronary syndrome, trauma, anaphylaxis)
• Already receiving IV antibiotics (“Hospital in the home” patients)
• Cystic Fibrosis
• Transplant recipient of solid organs
• Cancer patients receiving active treatment
• Patient has been an in-patient at a health-care facility in the last 7-days

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 will be placed on Emergency vehicles. After assessment and review of the inclusion/exclusion criteria, all eligible patients will be enrolled, and a peripheral blood culture drawn. The patient will subsequently be randomised to either paramedic administered 2g IV ceftriaxone or standard care. All patients will then be transported to a participating hospital.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software - Microsoft Excel (i.e. computerised sequence generation).
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2019
Actual
31/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
110
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15159 0
The Alfred - Melbourne
Recruitment hospital [2] 15160 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment postcode(s) [1] 28454 0
3004 - Melbourne
Recruitment postcode(s) [2] 28455 0
3550 - Bendigo

Funding & Sponsors
Funding source category [1] 298524 0
Government body
Name [1] 298524 0
Ambulance Victoria
Country [1] 298524 0
Australia
Primary sponsor type
Government body
Name
Ambulance Victoria
Address
375 Manningham Road
Doncaster VIC 3108
Country
Australia
Secondary sponsor category [1] 297672 0
None
Name [1] 297672 0
Address [1] 297672 0
Country [1] 297672 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299502 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 299502 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 299502 0
Australia
Date submitted for ethics approval [1] 299502 0
31/01/2018
Approval date [1] 299502 0
22/02/2018
Ethics approval number [1] 299502 0

Summary
Brief summary
In patients with severe sepsis, we aim to conduct a Phase 2, prospective, randomised controlled trial of intravenous antibiotics administered by paramedics in the prehospital setting, compared with standard care.
Sepsis is a common reason for presentation to an emergency department and has an annual incidence in adults of up to 300 cases per 100,000 persons per year. It is known that patients in the community with severe sepsis are more likely to arrive at hospital by ambulance than by other means.
Importantly, existing evidence from observational studies suggests that increased time to administration of antibiotics in these patients has a significant impact on mortality. However there is currently a considerable period of time between arrival of the patient with sepsis at the emergency department and administration of antibiotics.
As such, this study aims to test the hypothesis that, in patients with severe sepsis when evaluated by paramedics, prehospital administration of antibiotics will result in a significant reduction in the time to appropriate antibiotic treatment when compared with standard care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80638 0
Prof Stephen Bernard
Address 80638 0
Ambulance Victoria
375 Manningham Road
Doncaster VIC 3108
Country 80638 0
Australia
Phone 80638 0
+61 3 9840 3500
Fax 80638 0
Email 80638 0
[email protected]
Contact person for public queries
Name 80639 0
Prof Stephen Bernard
Address 80639 0
Ambulance Victoria
375 Manningham Road
Doncaster VIC 3108
Country 80639 0
Australia
Phone 80639 0
+61 3 9840 3500
Fax 80639 0
Email 80639 0
[email protected]
Contact person for scientific queries
Name 80640 0
Prof Andrew Udy
Address 80640 0
Australian and New Zealand Intensive Care Research Centre, Monash University
553 St Kilda Road, Melbourne, VIC 3004
Country 80640 0
Australia
Phone 80640 0
+61 3 9840 3500
Fax 80640 0
Email 80640 0
[email protected]

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
SourceTitleYear of PublicationDOI
Dimensions AIA Comparison of Australasian Jurisdictional Ambulance Services’ Paramedic Clinical Practice Guidelines Series: Adult Sepsis2021https://doi.org/10.33151/ajp.18.932
N.B. These documents automatically identified may not have been verified by the study sponsor.