Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000624684
Ethics application status
Approved
Date submitted
24/05/2023
Date registered
7/06/2023
Date last updated
28/05/2024
Date data sharing statement initially provided
7/06/2023
Date results information initially provided
28/05/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot trial of single versus dual diuretic therapy in the intensive care unit
Scientific title
A pilot trial of single versus dual diuretic therapy in the intensive care unit
Secondary ID [1] 309727 0
nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
critical care
 330118 0
Condition category
Condition code
Renal and Urogenital 327000 327000 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Throughout the patient's admission to the intensive care unit and at the time the treating intensive care doctor has decided to administer an intravenous diuretic, a single intravenous bolus of 40 mg furosemide and 500 mg acetazolamide will be given with the effects monitored via medical record audit.
Intervention code [1] 326166 0
Treatment: Drugs
Comparator / control treatment
Throughout the patient's admission to the intensive care unit and at the time the treating intensive care doctor has decided to administer an intravenous diuretic, a single intravenous bolus of 40 mg furosemide will be given with the effects monitored via medical record audit.
Control group
Active

Outcomes
Primary outcome [1] 334859 0
urinary output after diuretic administration
Timepoint [1] 334859 0
Total urinary outcome in the 6 hours after diuretic administration while the patient is in the intensive care unit obtained from the medical record.
Secondary outcome [1] 422259 0
Serum bicarbonate level change
Timepoint [1] 422259 0
Change in serum bicarbonate level assessed immediately before and then 6-hours after diuretic administration while the patient is in the intensive care unit obtained from the medical record.
Secondary outcome [2] 422260 0
Serum base excess change
Timepoint [2] 422260 0
Change in serum base excess level assessed immediately before and then 6-hours after diuretic administration while the patient is in the intensive care unit obtained from the medical record.
Secondary outcome [3] 422261 0
Urinary chloride level change
Timepoint [3] 422261 0
Change in urinary chloride level assessed immediately before and then 6-hours after diuretic administration while the patient is in the intensive care unit obtained from the medical record.
Secondary outcome [4] 422262 0
Serum sodium level change
Timepoint [4] 422262 0
Change in serum sodium level assessed immediately before and then 6-hours after diuretic administration while the patient is in the intensive care unit obtained from the medical record.
Secondary outcome [5] 422263 0
Fluid balance effect
Timepoint [5] 422263 0
Change in fluid balance assessed immediately before and then 6-hours after diuretic administration while the patient is in the intensive care unit obtained from the medical record.

Eligibility
Key inclusion criteria
Adults aged 18 years or above
Physician decision to administer an intravenous diuretic;
Anticipated length of stay of more than 24 hours after intervention administration
Existing intra-arterial or central venous catheter
Existing indwelling urinary catheter
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known allergy to furosemide or acetazolamide or other sulphonamides
known end-stage renal failure
Dose of any diuretic in the preceding 6 hours
Significant acid-base disturbance at time of enrolment (pH less than 7.25 or greater than 7.5)
Treatment with renal replacement therapy during this intensive care stay
Previously enrolled in this study

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
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Other design features
No other diuretics are to be administered to patients during the 6-hour study period following administration of diuretic therapy, unless clinically indicated by the patient’s treating intensive care unit physician.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on previous studies and observations in the intensive care, we assumed that using an alpha of 0.05 for significance, a study of 28 patients would have a greater than 80% power to detect a difference in urinary based on an expected urinary output of 500 ml over 6 hours (SD 200 ml) with furosemide and an increase to 710 ml with the addition of acetazolamide. We have increased the sample size to 30 patients to account for possible withdrawal of consent or data missingness.

A p value below 0.05 will be considered as statistically significant. Continuous variables will be reported as median with interquartile range in brackets; categorical variables are reported as count with percentage in parenthesis.

Comparisons between study arms will be performed using Fisher’s exact test for categorical variables, and the Wilcoxon-Mann-Whitney test for continuous variables. To assess the effects of each study drug on serum and urinary electrolytes, we will compared their value at 6 hours of drug administration, and their change from baseline, using the Wilcoxon-Mann-Whitney test. We will also compare the effects of study drugs on hourly UO and cumulative fluid balance over 6 hours, using linear mixed effects regression model, accounting for the repetition and the interdependence of hourly assessments in a given individual. When relevant, we will complete this analysis by performing a pairwise comparison of hourly urinary output and cumulative fluid balance at each time point between study groups, using the Tukey adjusting method. A P less than 0.05 will considered statistically significant.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
23/05/2023
Date of last participant enrolment
Anticipated
31/12/2023
Actual
9/02/2024
Date of last data collection
Anticipated
30/06/2024
Actual
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24794 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 40435 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 313918 0
Hospital
Name [1] 313918 0
Austin Health
Country [1] 313918 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Austin Health
145 Studley Road
Heidelberg Victoria 3084
Country
Australia
Secondary sponsor category [1] 315779 0
Individual
Name [1] 315779 0
Professor Rinaldo Bellomo
Address [1] 315779 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg Victoria 3084
Country [1] 315779 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313065 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 313065 0
Austin Health
145 Studley Road
Heidelberg Victoria 3084
Ethics committee country [1] 313065 0
Australia
Date submitted for ethics approval [1] 313065 0
24/03/2023
Approval date [1] 313065 0
14/04/2023
Ethics approval number [1] 313065 0
HREC/84325/Austin-2022

Summary
Brief summary
Diuretics are commonly used in the intensive care unit with the aim of achieving a negative fluid balance; yet remarkably little is known about their pharmacodynamic properties in critically ill patients. The most frequently used class of diuretic drugs are the loop diuretics, and furosemide is the most commonly used loop diuretic. However, loop diuretics may have a number of undesirable side effects, including electrolyte derangements and metabolic alkalosis. This pilot trial will randomly allocate 40 patients (20 in each arm) to receive Furosemide only or Furosemide and Acetazolamide. The primary outcome is urinary output occurring in the 6 hours after diuretic administration while in the intensive care unit. Results will inform future clinical trials and the outcomes that will be selected for these future trials.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126866 0
Prof Rinaldo Bellomo
Address 126866 0
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg Victoria 3084
Country 126866 0
Australia
Phone 126866 0
+61394965992
Fax 126866 0
+61394963932
Email 126866 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 126867 0
Prof Rinaldo Bellomo
Address 126867 0
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg Victoria 3084
Country 126867 0
Australia
Phone 126867 0
+61394965992
Fax 126867 0
+61394963932
Email 126867 0
rinaldo.bellomo@austin.org.au
Contact person for scientific queries
Name 126868 0
Prof Rinaldo Bellomo
Address 126868 0
Director, Intensive Care Research
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg Victoria 3084
Country 126868 0
Australia
Phone 126868 0
+61394965992
Fax 126868 0
+61394963932
Email 126868 0
rinaldo.bellomo@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is a pilot trial and results with be used to plan future trials and hypothesis-generating.


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.