Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000327583
Ethics application status
Approved
Date submitted
15/02/2024
Date registered
25/03/2024
Date last updated
25/03/2024
Date data sharing statement initially provided
25/03/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Intervention with concentrated albumin for resuscitation of undifferentiated sepsis - Multi Day
Scientific title
Intervention with concentrated albumin for resuscitation of undifferentiated sepsis in Emergency Department Patients - Multi Day: A randomised controlled trial
Secondary ID [1] 311549 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ICARUS-MD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
sepsis 332906 0
Condition category
Condition code
Emergency medicine 329620 329620 0 0
Resuscitation
Infection 329621 329621 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Immediately after randomisation, the intervention group will receive 20% human serum albumin, infused intravenously at 100mL/hr over 4 hours, concurrently with standard crystalloid-based fluid therapy as deemed appropriate by the treating emergency team.

Over the next 10 days (or until discharge if the patient is discharged prior to 10 days), patients will receive a daily dose of 20% albumin, with the dose determined by the serum albumin concentration in the preceding 24 hours. Specifically, patients will receive:

300mL if serum albumin is <25g/L,
200mL if serum albumin is >=25 and <30g/L
100mL if serum albumin unmeasured within 48hrs, or previous measurement <35g/L
No dose if previous serum albumin >=35g/L

Adherence to the intervention will be monitored using the patient medication chart. Initial doses of crystalloid and albumin will be administered while the patient is in the Emergency Department. This time period is on average 4-6 hours. The remaining doses will be administered while the patient is in a ward within the hospital.

Crystalloid fluid therapies will be administered to patients in both study arms according to evidence-based guidelines such as those disseminated by the Surviving Sepsis Campaign. Modern guidelines advocate discrete bolus fluid therapy (most clinicians utilise volumes of 500mL) with frequent reassessment, clinical examination and evaluation of available physiologic variables (heart rate, blood pressure, arterial oxygen saturation, respiratory rate, temperature, urine output, and others, as available) as well as other non-invasive (e.g., capnography) or invasive monitoring (e.g., arterial blood pressure), as available.
Intervention code [1] 328002 0
Treatment: Drugs
Comparator / control treatment
The standard care group will receive crystalloid solutions as required in accordance with standard care, and no albumin. The type of crystalloid fluid administered will be at the discretion of the treating clinician. Crystalloid fluid therapies will be administered to patients in both study arms according to evidence-based guidelines such as those disseminated by the Surviving Sepsis Campaign. Modern guidelines advocate discrete bolus fluid therapy (most clinicians utilise volumes of 500mL intravenously) with frequent reassessment, clinical examination and evaluation of available physiologic variables (heart rate, blood pressure, arterial oxygen saturation, respiratory rate, temperature, urine output, and others, as available) as well as other non-invasive or invasive monitoring, as available.

Crystalloid will be administered while the patient is in the Emergency Department. This time period is on average 4-6 hours. Crystalloid may also be provided throughout the hospital stay as required standard care at the discretion of inpatient treating teams.
Control group
Active

Outcomes
Primary outcome [1] 337411 0
Organ function
Timepoint [1] 337411 0
24h, 48h, 72h, 5 days, 7 days and 10 days post randomisation.
Secondary outcome [1] 431765 0
Rate of change of SOFA
Timepoint [1] 431765 0
From baseline to discharge from acute care (maximum 10 days)
Secondary outcome [2] 431766 0
ICU admission
Timepoint [2] 431766 0
At any time throughout the patient hospital admission
Secondary outcome [3] 431767 0
ICU length of stay
Timepoint [3] 431767 0
At time of discharge from ICU
Secondary outcome [4] 431769 0
Emergency Department length of stay
Timepoint [4] 431769 0
at time of discharge from the Emergency Department
Secondary outcome [5] 431770 0
Hospital length of stay
Timepoint [5] 431770 0
At time of discharge from hospital
Secondary outcome [6] 431771 0
Total fluid administered
Timepoint [6] 431771 0
24 hours, 48 hours, 72 hours, 5 days, 7 days and 10 days post randomisation
Secondary outcome [7] 431772 0
Requirement for vasoactive agents
Timepoint [7] 431772 0
During the hospital admission
Secondary outcome [8] 431773 0
Renal replacement therapy
Timepoint [8] 431773 0
During the hospital admission

Eligibility
Key inclusion criteria
Adult ED patients (greater than or equal to 18 years) with:
1) Systolic blood pressure (SBP) <90mmHg within 8 hours of triage (or lactate greater than or equal to 4)
2) Proven or presumed infection. Patients with presumed infection will be those where the treating senior treating emergency physician deems infection the most likely cause for the patient presentation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Jehovah’s Witness
2) Known adverse reaction to albumin administration
3) Terminal state - death seems imminent and inevitable
4) Pathological conditions in which albumin administration is clinically indicated (hepatic cirrhosis with ascites, intestinal malabsorption syndrome, nephrotic syndrome)
5) Acute congestive heart failure
6) Acute head injury
7) Inter-hospital transfer
8) Prior enrolment in the trial within the past 90 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)
Allocation involves contacting the holder of the allocation schedule who is off-site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomisation sequence will be generated using R software. Permuted block randomisation with variable block sizes will be used
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
A description of baseline characteristics of trial participants will be presented by treatment group. Discrete data will be presented as number and % of treatment group. Continuous data will be presented as mean (SD) or median (interquartile range, IQR). Data for the primary outcome (total SOFA) will be reported by treatment group as either mean (SD) or median (IQR).

Rate-of-change in total SOFA (secondary outcome) will be examined using generalized linear modelling with the vector of responses (including baseline) treated as random outcomes. Treatment will be included in the model as a fixed outcome. The remaining secondary outcomes (SOFA scores at various timepoints, ED and hospital LOS, total fluid, vasopressor requirements) will be reported as descriptive statistics by treatment group. For continuous data, the difference between group means or group medians will be calculated with 95% confidence intervals. For ED and hospital LOS data, time-to-event analyses will be used to compare groups to allow for any censoring if there is in-hospital mortality. For categorical data, the risk difference and risk ratio will be reported with 95% confidence intervals of the difference. With the primary analysis being intention-to-treat, we will conduct a per-protocol analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/01/2024
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
10/01/2026
Actual
Sample size
Target
324
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 42057 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 315844 0
Charities/Societies/Foundations
Name [1] 315844 0
Emergency Medicine Foundation
Country [1] 315844 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Women's Hospital
Address
Country
Australia
Secondary sponsor category [1] 317975 0
None
Name [1] 317975 0
Address [1] 317975 0
Country [1] 317975 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314700 0
Metro North Health Human Research Ethics Committee A
Ethics committee address [1] 314700 0
Ethics committee country [1] 314700 0
Australia
Date submitted for ethics approval [1] 314700 0
10/10/2022
Approval date [1] 314700 0
20/10/2022
Ethics approval number [1] 314700 0
AM/2022/MNHA/67432

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

Contacts
Principal investigator
Name 132438 0
Dr Julian Williams
Address 132438 0
Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029
Country 132438 0
Australia
Phone 132438 0
+61 7 3646 7901
Fax 132438 0
Email 132438 0
julian.williams@health.qld.gov.au
Contact person for public queries
Name 132439 0
Julian Williams
Address 132439 0
Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029
Country 132439 0
Australia
Phone 132439 0
+61 7 3646 7901
Fax 132439 0
Email 132439 0
julian.williams@health.qld.gov.au
Contact person for scientific queries
Name 132440 0
Julian Williams
Address 132440 0
Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029
Country 132440 0
Australia
Phone 132440 0
+61 7 3646 7901
Fax 132440 0
Email 132440 0
julian.williams@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Private health information can not be routinely shared due to privacy legislation and hospital policy. However, individuals may contact the principal investigator for information about applying to the hospital for the data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21656Study protocol  jhgreensladeconsulting@gmail.com
21657Analytic code  jhgreensladeconsulting@gmail.com
21658Informed consent form  jhgreensladeconsulting@gmail.com
21659Data dictionary  jhgreensladeconsulting@gmail.com
21660Ethical approval  jhgreensladeconsulting@gmail.com



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.