Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001043820
Ethics application status
Approved
Date submitted
24/07/2021
Date registered
9/08/2021
Date last updated
16/06/2024
Date data sharing statement initially provided
9/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Acute Renal effects of Angiotensin II Management In Shock (ARAMIS-2)
Scientific title
A phase 2b randomised controlled trial of the renal effects of angiotensin II versus noradrenaline in critically ill patients with vasodilatory shock
Secondary ID [1] 304865 0
None
Universal Trial Number (UTN)
Trial acronym
ARAMIS-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vasodilatory shock 322977 0
Condition category
Condition code
Renal and Urogenital 320547 320547 0 0
Kidney disease
Cardiovascular 320548 320548 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Angiotensin II administered continuously via intravenous infusion at a dose range of 1.25-40 ng/kg/min, with the administered dose titrated to achieve a MAP >65 until resolution of shock or for a maximum of 7 days. After 7 days, patients will be transitioned to noradrenaline as per hospital protocol.

Patients in the intervention arm may receive noradrenaline, metaraminol, and/or vasopressin prior to angiotensin II where this therapy was initiated in the operating theatre, emergency department, or on the ward prior to ICU transfer. However, patients who have received >24 hours of an alternative vasopressor prior to enrolment are ineligible for the study.

Adherence to the intervention will be monitored using the electronic heart record.
Intervention code [1] 321255 0
Treatment: Drugs
Comparator / control treatment
Noradrenaline administered continuously via intravenous infusion at a dose range of 1-50 mcg/min with the administered dose titrated to achieve a MAP >65 until resolution of shock.
Control group
Active

Outcomes
Primary outcome [1] 328371 0
Serum creatinine (umol/L)
Timepoint [1] 328371 0
Measured at baseline and every 4-6 hours post-commencement of infusion for a maximum of 7 days or until ICU discharge
Secondary outcome [1] 398775 0
The number of patients who develop either new or progressive KDIGO acute kidney injury (as assessed using biochemical data obtained during hospitalisation) following initiation of intervention or control infusions (this is a composite outcome).
Timepoint [1] 398775 0
7 days post-commencement of infusion
Secondary outcome [2] 398776 0
The number of patients who require renal replacement therapy following initiation of intervention or control infusions as assessed using the patient medical record
Timepoint [2] 398776 0
7 days post-commencement of infusion
Secondary outcome [3] 398777 0
Average daily urine output (L/day) as assessed using the patient medical record
Timepoint [3] 398777 0
Daily for 7 days post-commencement of infusion
Secondary outcome [4] 398778 0
Cumulative fluid balance (L) as assessed using the patient medical record
Timepoint [4] 398778 0
7 days post-commencement of infusion
Secondary outcome [5] 398779 0
The number of patients who require invasive ventilation following initiation of intervention or control infusions as assessed using the patient medical record
Timepoint [5] 398779 0
7 days post-commencement of infusion
Secondary outcome [6] 398780 0
ICU length of stay as assessed using the patient medical record
Timepoint [6] 398780 0
Patient discharge from ICU
Secondary outcome [7] 398781 0
Hospital length of stay as assessed using the patient medical record
Timepoint [7] 398781 0
Patient discharge from hospital
Secondary outcome [8] 398782 0
Days alive and free of renal replacement therapy (composite) as assessed using the patient medical record
Timepoint [8] 398782 0
28 days post-commencement of infusion
Secondary outcome [9] 398783 0
The number of patients who die during their ICU stay as assessed using the patient medical record
Timepoint [9] 398783 0
ICU discharge
Secondary outcome [10] 398784 0
The number of patients who die in hospital as assessed using the patient medical record
Timepoint [10] 398784 0
Hospital discharge
Secondary outcome [11] 398785 0
The number of patients who die within 28 days of initiation of the infusion as assessed using the patient medical record
Timepoint [11] 398785 0
28 days post-commencement of infusion
Secondary outcome [12] 398786 0
The number of patients who develop a thromboembolic event as assessed using the patient medical record
Timepoint [12] 398786 0
7 days post-commencement of infusion

Eligibility
Key inclusion criteria
• Adults aged 18+ years
• Vasodilatory shock (MAP <65 mmHg)
• Central venous access and an arterial line present
• Indwelling urinary catheter
• Expected to require vasopressor support for at least 24 hours
• Informed consent provided by the patient or medical treatment decision-maker
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Cardiac surgery patients
• >24 hours noradrenaline, metaraminol or vasopressin prior to enrolment
• Chronic haemodialysis or peritoneal dialysis
• Not expected to receive venous thromboembolism prophylaxis in the next 72 hours
• Expected survival <24 hours
• Suspected or confirmed pregnancy

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)
A centralised, web-based system (REDCap) will be employed, allowing 24-hour enrolment and random allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The random allocation sequence will be generated using a computer software program and embedded into the REDCap system. Site investigators, site research coordinators, and study participants will not have access to the allocation sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis will be performed using computerized software (Stata MP/16.0, StataCorp, College Station, Texas, USA). Baseline characteristics will be reported as frequencies and percentages, means and standard deviation, or medians and interquartile ranges. Summary statistics to compare baseline characteristics will include t-test, chi squared test, and Wilcoxon rank sum test, as dictated by data type. The primary outcome will be reported using a multilevel mixed effect linear regression model. Secondary outcomes will be explored using linear (continuous outcomes) and logistic (binary outcomes) regression models. No imputation will be performed for missing data. Pre-specified secondary analyses will examine whether baseline and 24 hour renin level can identify angiotensin II patients most likely to benefit. For all analyses, a two-sided p-value <0.05 will be considered significant.

Based on the small available number of published studies, we anticipate the mean peak serum creatinine level will be 140 umol/L with an expected standard deviation of approximately 30 umol/L. To detect a 10% decrease in mean creatinine with 80% power and an alpha of 0.05, we will need a sample size of at least 144 patients. Therefore, the recruitment of 150 patients will be targeted to ensure the study is adequately powered.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/10/2021
Actual
21/10/2021
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
31/03/2026
Actual
Sample size
Target
150
Accrual to date
78
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 20073 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 26681 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 26682 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [4] 26683 0
The Alfred - Melbourne
Recruitment hospital [5] 26684 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [6] 26685 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 26686 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 26687 0
Nepean Hospital - Kingswood
Recruitment hospital [9] 26688 0
Caboolture Hospital - Caboolture
Recruitment postcode(s) [1] 34779 0
3084 - Heidelberg
Recruitment postcode(s) [2] 42722 0
3050 - Parkville
Recruitment postcode(s) [3] 42723 0
3168 - Clayton
Recruitment postcode(s) [4] 42724 0
3004 - Melbourne
Recruitment postcode(s) [5] 42725 0
3065 - Fitzroy
Recruitment postcode(s) [6] 42726 0
5042 - Bedford Park
Recruitment postcode(s) [7] 42727 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 42728 0
2747 - Kingswood
Recruitment postcode(s) [9] 42729 0
4510 - Caboolture

Funding & Sponsors
Funding source category [1] 309240 0
Hospital
Name [1] 309240 0
Austin Health Anaesthesia and Intensive Care Special Purpose Fund
Country [1] 309240 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Road, Heidelberg, 3084, VIC
Country
Australia
Secondary sponsor category [1] 310206 0
Individual
Name [1] 310206 0
Rinaldo Bellomo
Address [1] 310206 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country [1] 310206 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309087 0
Austin Health
Ethics committee address [1] 309087 0
Ethics committee country [1] 309087 0
Australia
Date submitted for ethics approval [1] 309087 0
05/05/2021
Approval date [1] 309087 0
01/07/2021
Ethics approval number [1] 309087 0

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

Contacts
Principal investigator
Name 112926 0
Dr Emily See
Address 112926 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country 112926 0
Australia
Phone 112926 0
+61 3 9496 6666
Fax 112926 0
Email 112926 0
[email protected]
Contact person for public queries
Name 112927 0
Emily See
Address 112927 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country 112927 0
Australia
Phone 112927 0
+61 3 9496 6666
Fax 112927 0
Email 112927 0
[email protected]
Contact person for scientific queries
Name 112928 0
Emily See
Address 112928 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country 112928 0
Australia
Phone 112928 0
+61 3 9496 6666
Fax 112928 0
Email 112928 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
Ethics approval not sought for sharing of patient data


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.