Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000364572
Ethics application status
Approved
Date submitted
13/12/2023
Date registered
28/03/2024
Date last updated
28/03/2024
Date data sharing statement initially provided
28/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Terlipressin for the treatment of refractory hypotension in patients otherwise ready for discharge.
Scientific title
Terlipressin for the treatment of refractory hypotension in patients otherwise ready for discharge.
Secondary ID [1] 311175 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypotension 332349 0
Cardiovascular disease
 332350 0
Condition category
Condition code
Cardiovascular 329060 329060 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 329153 329153 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be randomized to receive 1mg q6h of terlipressin IV The dose would be given once every 6 hrs until ready for ICU discharge. If there is no change in the noradrenaline dose at 12 hrs, the dose of the study drug would be increased to 2mg every 6 hrs until ready for ICU discharge., The adherence to intervention would be monitored by looking at the ICU flow chart which gets updated hourly. The bed side nurse will be educated as well, and the study team will ensure compliance. No blood tests are required.
Clear colourless aqueous solution, - 5 mL of injection solution contains 1 mg terlipressin acetate equivalent to 0.85 mg terlipressin.
The rationale for using 1 mg is based on the typical dose that is the most commonly used starting dose.
ICU standard clinical care will continue for treatment of refractory hypotension requiring IV vasopressor treatment.
ICU Standard of care includes bedside monitoring of the blood pressure and achieving/maintaining the mean arterial pressure set by the clinician with or without the use of vasoactive agents.
Intervention code [1] 327620 0
Treatment: Drugs
Comparator / control treatment
Saline (5mL) will be used as a placebo in the control group.
ICU standard clinical care will continue for treatment of refractory hypotension requiring IV vasopressor treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 336863 0
Time from initiation of study drug until discontinuation of IV vasopressors drug until discontinuation of IV vasopressors
Timepoint [1] 336863 0
Discontinuation of IV vasopressors.
immediately after discontinuation of IV vasopressors.
Primary outcome [2] 336864 0
Time from study drug administration to ICU discharge readiness
Timepoint [2] 336864 0
When the patients are ready for discharge as deemed by the treating clinician.
Secondary outcome [1] 429923 0
Rates of ICU readmission,
Timepoint [1] 429923 0
Daily Until hospital discharge
Secondary outcome [2] 430301 0
Length of stay (LOS) in days.
Timepoint [2] 430301 0
Daily until hospital discharge.
The data will be collected through Webpas (Online patient administrative system and electronic medical records.
Secondary outcome [3] 430302 0
Incidence of adverse reactions from study medication.
The data will be collected via phyical medical records and electronic medical records.
Timepoint [3] 430302 0
Daily until hospital discharge.

Eligibility
Key inclusion criteria
• Adults (>=18 years of age)
• Admitted to the SCGH ICU
• Requiring IV vasopressors (metaraminol, noradrenaline, central or peripheral) for more than 6 hours
• Rate of less than 10 mcg/min of noradrenaline
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Inadequate tissue oxygenation ((lactate > 2 mmol plus any acute rise in creatinine by at least 50 mmol/l within 24 hours), or acute rise in ALT > 3x)
• Mesenteric ischaemia or recent laparotomy
• Hypovolemic shock (uncorrected) or hypotension due to adrenal insufficiency (if a serum cortisol assessment had been performed for clinical reasons
• Severe organic heart disease (EF < 35%, recent MI or heart failure (last month))
• Uncontrolled hypertension
• Conditions that may be exacerbated by fluid overload (chronic renal failure, cardiac disease)
• Uncorrected hypokalemia (<3) or hypomagnesemia (< 0.6) as may prolong QT interval
• Hyponatraemia – Na <130
• Women between the ages of 18-55 who have not had a surgical hysterectomy will only be eligible or for inclusion if they have a negative urine pregnancy test.
• Pregnancy testing will not need to be repeated if there is a documented negative urine pregnancy test that was obtained within 7 days prior to starting study drug, provided the woman was an ICU inpatient throughout that period of time.

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)
Randomisation module will be used from RedCAP
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 receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 0
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Baseline data will be described: continuous data will expressed as mean (standard deviation) or median (interquartile range), as appropriate based on variable distribution; differences between groups will be compared using a t-test or Mann-Whitney U test, respectively. Categorical data will be presented as frequencies (proportions); differences between groups will be analysed using a chi square or Fisher exact test, as appropriate. Differences between groups will be presented with 95% confidence intervals. Negative binomial regression models for the outcome of time to vasopressor discontinuation will be performed, including an interaction term between treatment group and subgroup; results are reported as incidence rate ratios with 95% confidence intervals. For time-to-event analyses, Kaplan-Meier curves and log-rank tests will be used to compare time to vasopressor discontinuation and ICU/hospital lengths of stay between groups, with adjustment for multiple testing. A two-sided p<0.05 will be considered statistically significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2024
Actual
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
31/01/2026
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25945 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 41778 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 315432 0
Hospital
Name [1] 315432 0
North Metropolitan Health Service Sir Charles Gairdner Hospital (ICU Research cost centre)
Country [1] 315432 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
10 Hospital Avenue, Nedlands, 60090 WA
Country
Australia
Secondary sponsor category [1] 317833 0
None
Name [1] 317833 0
Address [1] 317833 0
Country [1] 317833 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314343 0
Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee (EC00271)
Ethics committee address [1] 314343 0
Ethics committee country [1] 314343 0
Australia
Date submitted for ethics approval [1] 314343 0
16/06/2023
Approval date [1] 314343 0
14/09/2023
Ethics approval number [1] 314343 0

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

Contacts
Principal investigator
Name 131254 0
Dr Matthew Anstey
Address 131254 0
Sir Charles Gairdner Hospital, 10 Hospital Avenue, Nedlands, G block Level 4 ICU, 6009 WA
Country 131254 0
Australia
Phone 131254 0
+61 8645701010
Fax 131254 0
Email 131254 0
[email protected]
Contact person for public queries
Name 131255 0
Bhaumik Mevavala
Address 131255 0
Sir Charles Gairdner Hospital, 10 Hospital Avenue, Nedlands, G block Level 4 ICU, 6009 WA
Country 131255 0
Australia
Phone 131255 0
+61 864570072
Fax 131255 0
Email 131255 0
[email protected]
Contact person for scientific queries
Name 131256 0
Matthew Anstey
Address 131256 0
Sir Charles Gairdner Hospital, 10 Hospital Avenue, Nedlands, G block Level 4 ICU, 6009 WA
Country 131256 0
Australia
Phone 131256 0
+61 8645701010
Fax 131256 0
Email 131256 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
No additional documents have been identified.