ANZCTR - Registration

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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]

Nil known

Universal Trial Number (UTN)

Trial acronym

ICARUS-MD

Linked study record

Health condition

Health condition(s) or problem(s) studied:

sepsis

Condition category

Condition code

Emergency medicine

Resuscitation

Infection

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]

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]

Organ function

Timepoint [1]

24h, 48h, 72h, 5 days, 7 days and 10 days post randomisation.

Secondary outcome [1]

Rate of change of SOFA

Timepoint [1]

From baseline to discharge from acute care (maximum 10 days)

Secondary outcome [2]

ICU admission

Timepoint [2]

At any time throughout the patient hospital admission

Secondary outcome [3]

ICU length of stay

Timepoint [3]

At time of discharge from ICU

Secondary outcome [4]

Emergency Department length of stay

Timepoint [4]

at time of discharge from the Emergency Department

Secondary outcome [5]

Hospital length of stay

Timepoint [5]

At time of discharge from hospital

Secondary outcome [6]

Total fluid administered

Timepoint [6]

24 hours, 48 hours, 72 hours, 5 days, 7 days and 10 days post randomisation

Secondary outcome [7]

Requirement for vasoactive agents

Timepoint [7]

During the hospital admission

Secondary outcome [8]

Renal replacement therapy

Timepoint [8]

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?

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

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment postcode(s) [1]

4029 - Royal Brisbane Hospital

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Emergency Medicine Foundation

Address [1]

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Brisbane and Women's Hospital

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Metro North Health Human Research Ethics Committee A

Ethics committee address [1]

https://metronorth.health.qld.gov.au/research/ethics-and-governance/human-research-ethics-committee

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/10/2022

Approval date [1]

20/10/2022

Ethics approval number [1]

AM/2022/MNHA/67432

Summary

Brief summary

Research into improved management and treatment for patients with infection is essential for reducing such mortality. Individuals who present to the Emergency Department with severe infections are treated with fluids in the vein to maintain optimal blood volume, keep the heart working properly, and keep tissues well oxygenated. There are a number of fluids that Emergency Physicians can provide to patients, including crystalloids (water-based fluids that include salts and other water-soluble molecules), and albumin (a fluid manufactured from human plasma). 

Within this study, we will randomise patients with severe infection to receive either albumin or crystalloids. The aim is to determine whether albumin improves the patient’s outcome.. The results of the study will provide emergency doctors with important information about how to best treat patients with infections and potentially reduce the number of deaths.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Julian Williams

Address

Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029

Country

Australia

Phone

+61 7 3646 7901

Fax

[email protected]

Contact person for public queries

Name

Julian Williams

Address

Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029

Country

Australia

Phone

+61 7 3646 7901

Fax

[email protected]

Contact person for scientific queries

Name

Julian Williams

Address

Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029

Country

Australia

Phone

+61 7 3646 7901

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Email
21656	Study protocol	[email protected]
21657	Analytic code	[email protected]
21658	Informed consent form	[email protected]
21659	Data dictionary	[email protected]
21660	Ethical approval	[email protected]

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.

Trial Review

Documents added manually

Documents added automatically